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Chen J, Li L, Yin Q, Shen T. A review of epidemiology and clinical relevance of Hepatitis B virus genotypes and subgenotypes. Clin Res Hepatol Gastroenterol 2023; 47:102180. [PMID: 37479136 DOI: 10.1016/j.clinre.2023.102180] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/07/2023] [Accepted: 07/13/2023] [Indexed: 07/23/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a global public health burden, affecting nearly 300 million people around the world. Due to HBV population is considered to be represented as a viral quasispecies with genetic diversity, some reports showed that different genotypes of HBV have different viral effects, though the emergence of antiviral drugs that effectively inhibit viral replication, however, HBV infection has still not been eradicated and further research is needed. SUMMARY HBV has been classified into at least ten genotypes (A-J) and more than 40 subgenotypes based on an intergroup or intragroup nucleotide difference across the whole genome, respectively. Inter genotypic recombinants were also observed during the HBV evolution. HBV genotypes and subgenotypes have distinct ethno-geographical distributions, as well as evident differences in their biological characteristics. HBV genotypes and subgenotypes also have close association with disease severity, long-term clinical outcomes, and response to antiviral therapy. KEYMESSAGES In this review, we up-dated the epidemiological characteristics, clinical features and prognosis of HBV infection with dissimilar genotype/subgenotypes, to better understanding and developing individualized prevention and treatment strategies.
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Affiliation(s)
- Jing Chen
- Medical school, Kunming University of Science and Technology, Kunming, 650500, Yunnan Province, PR China; Department of Pulmonary and Critical Care Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Institute of Basic and Clinical Medicine, The First People's Hospital of Yunnan Province, Kunming, 650032, PR China
| | - Li Li
- Department of Pulmonary and Critical Care Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Institute of Basic and Clinical Medicine, The First People's Hospital of Yunnan Province, Kunming, 650032, PR China
| | - Qi Yin
- Medical school, Kunming University of Science and Technology, Kunming, 650500, Yunnan Province, PR China; Department of Pulmonary and Critical Care Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Institute of Basic and Clinical Medicine, The First People's Hospital of Yunnan Province, Kunming, 650032, PR China
| | - Tao Shen
- Medical school, Kunming University of Science and Technology, Kunming, 650500, Yunnan Province, PR China; Department of Pulmonary and Critical Care Medicine, Yunnan Provincial Key Laboratory for Clinical Virology, Institute of Basic and Clinical Medicine, The First People's Hospital of Yunnan Province, Kunming, 650032, PR China; Department of Infectious Diseases and Hepatic Disease, Yunnan Province Innovation Team of Intestinal Microecology Related Disease Research and Technological Transformation, the First People's Hospital of Yunnan Province, Kunming 650032, PR China.
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Sant'Anna TB, Araujo NM. Hepatitis B Virus Genotype D: An Overview of Molecular Epidemiology, Evolutionary History, and Clinical Characteristics. Microorganisms 2023; 11:1101. [PMID: 37317074 PMCID: PMC10221421 DOI: 10.3390/microorganisms11051101] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 04/19/2023] [Accepted: 04/20/2023] [Indexed: 06/16/2023] Open
Abstract
The hepatitis B virus (HBV) genotype D (HBV/D) is the most extensively distributed genotype worldwide with distinct molecular and epidemiological features. This report provides an up-to-date review on the history of HBV/D subgenotyping and misclassifications, along with large-scale analysis of over 1000 HBV/D complete genome sequences, with the aim of gaining a thorough understanding of the global prevalence and geographic distribution of HBV/D subgenotypes. We have additionally explored recent paleogenomic findings, which facilitated the detection of HBV/D genomes dating back to the late Iron Age and provided new perspectives on the origins of modern HBV/D strains. Finally, reports on distinct disease outcomes and responses to antiviral therapy among HBV/D subgenotypes are discussed, further highlighting the complexity of this genotype and the importance of HBV subgenotyping in the management and treatment of hepatitis B.
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Affiliation(s)
- Thaís B Sant'Anna
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21041-250, RJ, Brazil
| | - Natalia M Araujo
- Laboratory of Molecular Virology and Parasitology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21041-250, RJ, Brazil
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Kafeero HM, Ndagire D, Ocama P, Kato CD, Wampande E, Walusansa A, Kajumbula H, Kateete D, Ssenku JE, Sendagire H. Mapping hepatitis B virus genotypes on the African continent from 1997 to 2021: a systematic review with meta-analysis. Sci Rep 2023; 13:5723. [PMID: 37029173 PMCID: PMC10082212 DOI: 10.1038/s41598-023-32865-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 04/04/2023] [Indexed: 04/09/2023] Open
Abstract
Hepatitis B virus (HBV) has ten genotypes (A-J) and over 40 sub-genotypes based on the divergence of ≥ 8% and 4 to < 8% in the complete genome respectively. These genotypes and sub-genotypes influence the disease prognosis, response to therapy and route of viral transmission. Besides, infection with mixed genotypes and recombinant genotypes has also been reported. This study aimed at mapping the de novo genotypes and correlate them with the immigration trends in order to inform future research on the underlying reasons for the relative distribution of HBV genotypes from a large sample size pooled from many primary studies. Data was extracted from 59 full research articles obtained from Scopus, PubMed, EMBASE, Willy library, African Journal Online (AJOL) and Google Scholar. Studies that investigated the genotypes, sub-genotypes, mixed genotypes and recombinant were included. The Z-test and regression were used for the analysis. The study protocol is registered with PROSPERO under the registration number CRD42022300220. Overall, genotype E had the highest pooled prevalence significantly higher than all the other genotypes (P < 0.001). By region, genotype A posted the highest pooled prevalence in eastern and southern Africa, E in west Africa and D in north Africa (P < 0.0001). Regarding the emerging genotypes B and C on the African continent, genotype B was significantly higher in south Africa than C (P < 0.001). In contrast, genotype C was significantly higher in east Africa than west Africa (P < 0.0001). The A1 and D/E were the most diverse sub-genotypes and genotype mixtures respectively. Finally, we observed a general progressive decrease in the prevalence of predominant genotypes but a progressive increase in the less dominant by region. Historical and recent continental and intercontinental migrations can provide a plausible explanation for the HBV genotype distribution pattern on the African continent.
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Affiliation(s)
- Hussein Mukasa Kafeero
- Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda.
- Department of Medical Microbiology, Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda, P. O Box 7689, Kampala, Uganda.
| | - Dorothy Ndagire
- Department of Plant Sciences, Microbiology and Biotechnology, College of Natural Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Ponsiano Ocama
- Department of Medicine, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Charles Drago Kato
- Department of Biomolecular Resources and Biolab Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Eddie Wampande
- Department of Biomolecular Resources and Biolab Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Abdul Walusansa
- Department of Medical Microbiology, Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda, P. O Box 7689, Kampala, Uganda
| | - Henry Kajumbula
- Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - David Kateete
- Department of Molecular Biology and Immunology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Jamilu E Ssenku
- Department of Plant Sciences, Microbiology and Biotechnology, College of Natural Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
| | - Hakim Sendagire
- Department of Medical Microbiology, College of Health Sciences, Makerere University, P. O Box 7062, Kampala, Uganda
- Department of Medical Microbiology, Habib Medical School, Faculty of Health Sciences, Islamic University in Uganda, P. O Box 7689, Kampala, Uganda
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Mathew A, Ismael N, Meeds H, Vubil A, Zicai AF, Mabunda N, Blackard JT. Hepatitis B virus genotypes and drug resistance mutations circulating in blood donors in Beira, Mozambique. PLoS One 2023; 18:e0281855. [PMID: 36795797 PMCID: PMC9934330 DOI: 10.1371/journal.pone.0281855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 02/02/2023] [Indexed: 02/17/2023] Open
Abstract
Hepatitis B virus (HBV) infects nearly 300 million people and is the leading cause of hepatitis and hepatocellular carcinoma worldwide. Despite the high burden of HBV in sub-Saharan Africa, countries such as Mozambique have limited data available on circulating HBV genotypes and the presence of drug resistance mutations. Blood donors from Beira, Mozambique were tested for HBV surface antigen (HBsAg) and HBV DNA at the Instituto Nacional de Saúde in Maputo, Mozambique. Regardless of HBsAg status, donors with detectable HBV DNA were evaluated for HBV genotype. PCR was performed with primers amplifying a 2.1-2.2 kilobase fragment of the HBV genome. PCR products were submitted for next generation sequencing (NGS), and consensus sequences were evaluated for HBV genotype, recombination, and the presence or absence of drug resistance mutations. Of the 1281 blood donors tested, 74 had quantifiable HBV DNA. The polymerase gene could be amplified from 45 of 58 (77.6%) individuals with chronic HBV infection and 12 of 16 (75%) with occult HBV infection. Among these 57, 51 (89.5%) sequences belonged to HBV genotype A1, while 6 (10.5%) were HBV genotype E. All genotype E sequences were E/A recombinants, and clustered separately from other genotype E references. Genotype A samples had a median viral load of 637 IU/mL, while genotype E samples had a median viral load of 476,084 IU/mL. No drug resistance mutations were observed in the consensus sequences. The current study demonstrates the genotypic diversity of HBV in blood donors in Mozambique, but the absence of dominant (consensus) drug resistance mutations. Studies in other at-risk populations are essential for understanding the epidemiology, risk of liver disease, and likelihood of treatment resistance in resource-limited settings.
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Affiliation(s)
- Ann Mathew
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America
| | - Nalia Ismael
- Instituto Nacional de Saúde, Marracuene, Mozambique
| | - Heidi Meeds
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America
| | - Adolfo Vubil
- Instituto Nacional de Saúde, Marracuene, Mozambique
| | | | | | - Jason T. Blackard
- Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, United States of America
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Belaiba Z, Ayouni K, Gdoura M, Kammoun Rebai W, Touzi H, Sadraoui A, Hammemi W, Yacoubi L, Abdelati S, Hamzaoui L, Msaddak Azzouz M, Chouikha A, Triki H. Whole genome analysis of hepatitis B virus before and during long-term therapy in chronic infected patients: Molecular characterization, impact on treatment and liver disease progression. Front Microbiol 2022; 13:1020147. [PMID: 36325017 PMCID: PMC9618822 DOI: 10.3389/fmicb.2022.1020147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 09/15/2022] [Indexed: 07/23/2023] Open
Abstract
Hepatitis B virus (HBV) infection remains a serious public health concern worldwide despite the availability of an efficient vaccine and the major improvements in antiviral treatments. The aim of the present study is to analyze the mutational profile of the HBV whole genome in ETV non-responder chronic HBV patients, in order to investigate antiviral drug resistance, immune escape, and liver disease progression to Liver Cirrhosis (LC) or Hepatocellular Carcinoma (HCC). Blood samples were collected from five chronic hepatitis B patients. For each patient, two plasma samples were collected, before and during the treatment. Whole genome sequencing was performed using Sanger technology. Phylogenetic analysis comparing the studied sequences with reference ones was used for genotyping. The mutational profile was analyzed by comparison with the reference sequence M32138. Genotyping showed that the studied strains belong to subgenotypes D1, D7, and D8. The mutational analysis showed high genetic variability. In the RT region of the polymerase gene, 28 amino acid (aa) mutations were detected. The most significant mutations were the pattern rtL180M + rtS202G + rtM204V, which confer treatment resistance. In the S gene, 35 mutations were detected namely sP120T, sT126S, sG130R, sY134F, sS193L, sI195M, and sL216stop were previously described to lead to vaccine, immunotherapy, and/or diagnosis escape. In the C gene, 34 mutations were found. In particular, cG1764A, cC1766G/T, cT1768A, and cC1773T in the BCP; cG1896A and cG1899A in the precore region and cT12S, cE64D, cA80T, and cP130Q in the core region were associated with disease progression to LC and/or HCC. Other mutations were associated with viral replication increase including cT1753V, cG1764A/T, cC1766G/T, cT1768A, and cC1788G in the BCP as well as cG1896A and cG1899A in the precore region. In the X gene, 30 aa substitutions were detected, of which substitutions xT36D, xP46S, xA47T, xI88F, xA102V, xI127T, xK130M, xV131I, and xF132Y were previously described to lead to LC and/or HCC disease progression. In conclusion, our results show high genetic variability in the long-term treatment of chronic HBV patients causing several effects. This could contribute to guiding national efforts to optimize relevant HBV treatment management in order to achieve the global hepatitis elimination goal by 2030.
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Affiliation(s)
- Zeineb Belaiba
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
- Research Laboratory “Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health,” LR20IPT02, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
| | - Kaouther Ayouni
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
- Research Laboratory “Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health,” LR20IPT02, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
| | - Mariem Gdoura
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
- Research Laboratory “Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health,” LR20IPT02, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
| | - Wafa Kammoun Rebai
- Laboratory of Biomedical Genomics and Oncogenetics (LR16IPT05), Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
| | - Henda Touzi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
| | - Amel Sadraoui
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
| | - Walid Hammemi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
| | - Lamia Yacoubi
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
| | - Salwa Abdelati
- Department of Gastroenterology, Polyclinic of CNSS, Sousse, Tunisia
| | - Lamine Hamzaoui
- Department of Gastroenterology, Hospital of Tahar Maamouri, Nabeul, Tunisia
| | | | - Anissa Chouikha
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
- Research Laboratory “Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health,” LR20IPT02, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
| | - Henda Triki
- Laboratory of Clinical Virology, WHO Reference Laboratory for Poliomyelitis and Measles in the Eastern Mediterranean Region, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
- Research Laboratory “Virus, Vectors and Hosts: One Health Approach and Technological Innovation for a Better Health,” LR20IPT02, Pasteur Institute of Tunis, University Tunis El Manar (UTM), Tunis, Tunisia
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Belyhun Y, Liebert UG, Maier M. Molecular epidemiology of hepatitis B virus among HIV co-infected and mono-infected cohorts in Northwest Ethiopia. Virol J 2022; 19:53. [PMID: 35331278 PMCID: PMC8944073 DOI: 10.1186/s12985-022-01774-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 03/02/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) infection is a particular concern in human immunodeficiency virus (HIV) infected individuals. In Ethiopia, detailed clinical and virological descriptions of HBV prevailing during HIV co-infection and symptomatic liver disease patients are lacking. The aim of this study was to investigate HBV virological characteristics from Ethiopian HBV/HIV co-infected and HBV mono-infected individuals. METHODS A total of 4105 sera from HIV positive individuals, liver disease patients, and blood donors were screened serologically for HBV. The overlapping polymerase/surface genome region of HBV from 180 infected individuals was extracted, amplified, and sequenced for genotypic analysis. RESULTS The HBsAg seroprevalence was detected 43% in liver disease patients, 8.4% in blood donors, and 6.7% in HIV/HBV co-infected individuals. The occult HBV prevalence was 3.7% in HIV/HBV co-infected individuals and 2.8% in blood donors with an overall prevalence rate of 3.4%. A phylogenetic analysis showed three HBV genotypes; A (61.1%), D (38.3%) and E (0.6%). Genotype A belongs to subtypes A1 (99.1%) and A9 (0.9%), but genotype D showed heterogeneous subtypes; D2 (63.8%) followed by D4 (21.7%), D1 (8.7%), D3 (4.3%), and D10 (1.4%). CONCLUSIONS The HIV/HBV co-infected individuals and blood donors showed lower HBsAg seroprevalence compared to liver diseases patients. Occult HBV prevalence showed no difference between HIV/HBV co-infected and blood donor groups. This study demonstrated predominance distribution of HBV subtypes A1 and D2 in northwest Ethiopia. The observed virological characteristics could contribute for evidence-based management of viral hepatitis in Ethiopia where antiretroviral therapy guidelines do not cater for viral hepatitis screening during HIV co-infection.
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Affiliation(s)
- Yeshambel Belyhun
- Department of Virology, Institute of Medical Microbiology, Leipzig University, Leipzig, Germany. .,School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
| | - Uwe Gerd Liebert
- Department of Virology, Institute of Medical Microbiology, Leipzig University, Leipzig, Germany
| | - Melanie Maier
- Department of Virology, Institute of Medical Microbiology, Leipzig University, Leipzig, Germany
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Liao H, Cai D, Sun Y. VirStrain: a strain identification tool for RNA viruses. Genome Biol 2022; 23:38. [PMID: 35101081 PMCID: PMC8801933 DOI: 10.1186/s13059-022-02609-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 01/12/2022] [Indexed: 12/18/2022] Open
Abstract
Viruses change constantly during replication, leading to high intra-species diversity. Although many changes are neutral or deleterious, some can confer on the virus different biological properties such as better adaptability. In addition, viral genotypes often have associated metadata, such as host residence, which can help with inferring viral transmission during pandemics. Thus, subspecies analysis can provide important insights into virus characterization. Here, we present VirStrain, a tool taking short reads as input with viral strain composition as output. We rigorously test VirStrain on multiple simulated and real virus sequencing datasets. VirStrain outperforms the state-of-the-art tools in both sensitivity and accuracy.
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Affiliation(s)
- Herui Liao
- Department of Electrical Engineering, City University of Hong Kong, Kowloon, China
| | - Dehan Cai
- Department of Electrical Engineering, City University of Hong Kong, Kowloon, China
| | - Yanni Sun
- Department of Electrical Engineering, City University of Hong Kong, Kowloon, China.
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Disproportionate Distribution of HBV Genotypes A and D and the Recombinant Genotype D/E in the High and Low HBV Endemic Regions of Uganda: A Wake-Up Call for Regional Specific HBV Management. Int J Hepatol 2022; 2022:3688547. [PMID: 35070455 PMCID: PMC8767397 DOI: 10.1155/2022/3688547] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 11/08/2021] [Accepted: 12/17/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) is the leading cause of liver-related diseases. In Uganda, there is a regional disparity in the HBV burden. Our study was aimed at establishing the circulating genotypes in a low and a high endemic region to give plausible explanations for the differences in regional burden and guide the future management of the disease. METHODS A total of 200 HBsAg-seropositive subjects were recruited into the study by convenience sampling. The HBsAg Rapid Test Strip (Healgen Scientific Limited Liability Company, Houston, TX77047- USA) was used to screen for HBsAg while the Roche machine (Roche, Basel Switzerland/Abbot Technologies (USA)) was used to determine the viral load. The Chemistry Analyzer B120 (Mindray, China) was used for chemistry analysis. For HBV genotyping, total DNA was extracted from whole blood using the QIAamp® DNA extraction kit. Nested PCR amplification was performed using Platinum Taq DNA Polymerase (Invitrogen Corporation, USA) to amplify the 400 bp HBV polymerase gene. Purification of nested PCR products was performed using Purelink PCR product purification kit (Life Technologies, USA). Automated DNA sequencing was performed using BigDye Terminator v3.1 Cycle Sequencing Kit on 3130 Genetic Analyzer (Applied Biosystems, USA). The NCBI HBV genotyping tool (https://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi) was used for determination of genotype for each HBV sequence. Pearson's chi-square, multinomial logistic regression, and Mann-Whitney U tests were used for the analysis. All the analyses were done using SPSS version 26.0 and MedCalc software version 19.1.3 at 95% CI. A p < 0.05 was considered statistically significant. RESULTS Majority of our study subjects were female (64.5%), youth (51.0%), and married (62.0%). Overall, genotype A was the most prevalent (46%). Genotype D and the recombinant genotype D/E were proportionately more distributed in the high endemic (38.2%) and low endemic (36.5%) regions, respectively. Genotype D was significantly more prevalent in the high endemic region and among the elderly (p < 0.05). Genotype D was significantly associated with elevated viral load and direct bilirubin (p < 0.05). The recombinant genotype D/E was significantly associated with elevated viral load (p < 0.05). Similarly, genotype A was significantly associated with elevated AST and GGT, lowered viral load, and normal direct bilirubin levels (p < 0.05). CONCLUSION There is disproportionate distribution of genotypes A and D and the recombinant genotype D/E in the low and high endemic regions of Uganda. This probably could explain the differences in endemicity of HBV in our country signifying the need for regional specific HBV management and control strategies.
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Ingasia LAO, Wose Kinge C, Kramvis A. Genotype E: The neglected genotype of hepatitis B virus. World J Hepatol 2021; 13:1875-1891. [PMID: 35069995 PMCID: PMC8727212 DOI: 10.4254/wjh.v13.i12.1875] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Revised: 06/15/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge status and gaps in its origin and evolution, natural history of infection, disease progression, response to antiviral therapy and vaccination are discussed. Genotype E is an African genotype, with unique molecular characteristics that is found mainly in Western and Central Africa and rarely outside Africa except in individuals of African descent. The low prevalence of this genotype in the African descendant populations in the New World, phylogeographic analyses, the low genetic diversity and evidence of remnants of genotype E in ancient HBV samples suggests the relatively recent re-introduction into the population. There is scarcity of information on the clinical and virological characteristics of genotype E-infected patients, disease progression and outcomes and efficacy of anti-HBV drugs. Individuals infected with genotype E have been characterised with high hepatitis B e antigen-positivity and high viral load with a lower end of treatment response to interferon-alpha. A minority of genotype E-infected participants have been included in studies in which treatment response was monitored. Of concern is that current guidelines do not consider patients infected with genotype E. Thus, there is an urgent need for further large-scale investigations into genotype E, the neglected genotype of HBV.
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Affiliation(s)
- Luicer Anne Olubayo Ingasia
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
| | - Constance Wose Kinge
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
- Department of Implementation Science, Right to Care, Johannesburg 0046, Gauteng, South Africa
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
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Ou G, He L, Wang L, Song J, Lai X, Tian X, Wang L, Zhang K, Zhang X, Deng J, Zhuang H, Xiang K, Li T. The Genotype (A to H) Dependent N-terminal Sequence of HBV Large Surface Protein Affects Viral Replication, Secretion and Infectivity. Front Microbiol 2021; 12:687785. [PMID: 34305848 PMCID: PMC8299529 DOI: 10.3389/fmicb.2021.687785] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 06/22/2021] [Indexed: 12/02/2022] Open
Abstract
Genetic variability has significant impacts on biological characteristics and pathogenicity of hepatitis B virus (HBV), in which the N-terminal sequence of the presurface 1 (preS1) region of HBV large surface protein (LHBs) displays genotype (GT) dependent genetic heterogeneity. However, the influence of this heterogeneity on its biological roles is largely unknown. By analyzing 6560 full-length genome sequences of GTA-GTH downloaded from HBVdb database, the preS1 N-terminal sequences were divided into four representative types, namely C-type (representative of GTA, GTB, and GTC), H-type (GTF and GTH), E-type (GTE and GTG), and D-type (GTD), respectively. We artificially substituted the preS1 N-termini of GTC and GTD plasmids or viral strains with each sequence of the four representative types. The roles of preS1 N-terminus on HBV replication, secretion and infectivity were investigated using HepG2 or HepG2-NTCP cells. In the transfection experiments, the results showed that the extracellular HBsAg levels and HBsAg secretion coefficients in D- and E-type strains were significantly higher than those in C- and H-type strains. D-type strain produced more extracellular HBV DNA than C-type strain. We further observed that D-, H-, and E-type strains increased the levels of intracellular replicative HBV DNAs, comparing with C-type strain. In the infection experiments, the levels of extracellular HBeAg, intracellular HBV total RNA and pgRNA/preC mRNA in D- and E-type strains were markedly higher than C and H-type ones. Our data suggest that the preS1 N-termini affect HBV replication, secretion and infectivity in a genotype dependent manner. The C- and H-type strains prefer to attenuate HBsAg secretion, while the strains of D- and E-type promoted infectivity. The existence and function of the intergenotypic shift of preS1 in naturally occurring recombination requires further investigation, as the data we acquired are mostly related to recombinant preS1 region between N-terminus of preS1 from genotypes A-H and the remaining preS1 portion of GTC or GTD.
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Affiliation(s)
- Guomin Ou
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Lingyuan He
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.,Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Luwei Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.,Department of Clinical Laboratory Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Ji Song
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Xinyuan Lai
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Xing Tian
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Lei Wang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Kai Zhang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Xuechao Zhang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Juan Deng
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Hui Zhuang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Kuanhui Xiang
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
| | - Tong Li
- Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
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11
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Marlet J, Lier C, Roch E, Moreau A, Combe B, Handala L, Lefeuvre S, Maugey M, Elkrief L, d'Alteroche L, Potier P, Brand D, Gaudy-Graffin C. Evolution and phenotypic characterization of whole HBV genome in compliant patients experiencing unexplained entecavir treatment failure. Antiviral Res 2021; 192:105106. [PMID: 34214504 DOI: 10.1016/j.antiviral.2021.105106] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 04/29/2021] [Accepted: 05/31/2021] [Indexed: 12/20/2022]
Abstract
Entecavir treatment failure can be observed in compliant patients despite an absence of detectable resistance mutations by Pol/RT Sanger sequencing. We hypothesized that these unexplained treatment failures could rely on other mechanisms of viral resistance, especially on mutations selected outside of the Pol/RT domain. Partial virological response to entecavir was observed in three patients treated with immunosuppressive drugs, without selection of Pol/RT resistance mutations. Mutations selected in the whole HBV genome during entecavir treatment and potentially associated with resistance were searched for using deep sequencing and characterized using a phenotypic resistance assay. Mutations Q206K (pre-core/core), Q120K (pre-S1/pre-S2, T-cell epitope) and A300E (spacer domain) were selected during entecavir treatment in patient #1 but were not associated with an increased level of resistance to entecavir or an increase in HBV replication capacity. Core promoter mutations T1753G, A1762T and G1764A were present as major mutations before and after treatment in patient #1. HBs Ag immune escape mutations were present as major mutations before and after treatment in patients #2 (sK122R, sT126I, sP127S and sG145R) and #3 (sM133I). We demonstrated that PVR to entecavir does not require selection of any resistance mutation in the whole HBV genome. Our results demonstrate that major mutations can be selected outside of the Pol/RT domain before or during entecavir treatment. These mutations could contribute to entecavir treatment failure by other mechanisms than an increased level of resistance.
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Affiliation(s)
- Julien Marlet
- INSERM U1259, Université de Tours et CHRU de Tours, France; Service de Bactériologie-Virologie-Hygiène, CHRU de Tours, France.
| | - Clément Lier
- INSERM U1259, Université de Tours et CHRU de Tours, France; Service de Bactériologie-Virologie-Hygiène, CHRU de Tours, France
| | | | - Alain Moreau
- INSERM U1259, Université de Tours et CHRU de Tours, France
| | - Benjamin Combe
- INSERM U1259, Université de Tours et CHRU de Tours, France
| | - Lynda Handala
- INSERM U1259, Université de Tours et CHRU de Tours, France
| | | | - Morgan Maugey
- INSERM U1259, Université de Tours et CHRU de Tours, France
| | - Laure Elkrief
- Service D'Hépato-gastroentérologie, CHRU de Tours, France
| | | | - Pascal Potier
- Service D'Hépato-gastroentérologie, CHR D'Orléans, France
| | - Denys Brand
- INSERM U1259, Université de Tours et CHRU de Tours, France; Service de Bactériologie-Virologie-Hygiène, CHRU de Tours, France
| | - Catherine Gaudy-Graffin
- INSERM U1259, Université de Tours et CHRU de Tours, France; Service de Bactériologie-Virologie-Hygiène, CHRU de Tours, France
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12
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Olusola BA, Faneye AO, Oluwasemowo OO, Motayo BO, Adebayo S, Oludiran-Ayoade AE, Aleru B, George UE, Oragwa AO. Profiles of mutations in hepatitis B virus surface and polymerase genes isolated from treatment-naïve Nigerians infected with genotype E. J Med Microbiol 2021; 70. [PMID: 33704041 DOI: 10.1099/jmm.0.001338] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Introduction. Hepatitis B virus (HBV) infection is the leading cause of hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HBV genotype E (HBV/E) is the predominant genotype in West Africa and has been linked epidemiologically with chronic and occult HBV infections as well as development of HCC. Mutations in the surface and polymerase genes of HBV have been associated with occult infection, drug resistance, vaccine escape, as well as HCC.Hypothesis/Gap Statement. There is limited data on the occurrence and patterns of mutations associated with occult infection, drug resistance, vaccine escape and HCC for HBV/E.Aim. This study characterized amino acid (aa) substitutions in the major hydrophilic (MHR) and reverse transcriptase (RT) regions of the surface and polymerase genes respectively of HBV sequences from a group of Nigerians with genotype E infection. The CpG islands of the PreC/C and PreS/S regions of these sequences were also described.Methodology. HBV surface and polymerase genes were detected using PCR techniques. Occurrence of new and previously described mutations in these genes were analysed using phylogenetic techniques.Results. Overall 13 HBV isolates were each sequenced for polymerase and surface genes mutations. Thirteen and nine PreS/S and PreC/C HBV genes respectively were analysed for CpG islands. Mutations in the MHR and a-determinants region of the S protein were discovered in eleven and nine of the 13 tested isolates respectively. These mutations were concomitant with aa changes in the RT functional domains of the isolates. Mutations associated with vaccine escape, occult infection and poor HCC prognosis were identified in HBV/E isolated in this study. Furthermore, all the isolates had at least one putative nucleotide analogue resistance mutations. Drug resistance mutations had the highest association with CpG islands.Conclusion. The results of this study contribute to further understanding of HBV variability in Nigeria and the West African region. This will aid the planning of adequate HBV immunization and treatment programmes for the countries in the region.
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Affiliation(s)
- Babatunde A Olusola
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Adedayo O Faneye
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | | | - Babatunde O Motayo
- Federal Medical Center, Abeokuta, Nigeria.,Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Sopeju Adebayo
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Ayomide E Oludiran-Ayoade
- Present address: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.,Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Bisola Aleru
- Department of Virology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Uwem E George
- Department of Biological Sciences, Redeemer's University, Ede, Osun State, Nigeria
| | - Arthur O Oragwa
- Department of Veterinary Microbiology, Faculty of Veterinary Medicine, University of Jos, Jos-Plateau State, Nigeria
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13
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Boyce CL, Willis S, Archampong TNA, Lartey M, Sagoe KW, Obo-Akwa A, Kenu E, Kwara A, Blackard JT. Identification of hepatitis B virus genotype A/E recombinants in Ghana. Virus Genes 2019; 55:707-712. [PMID: 31346975 PMCID: PMC6750976 DOI: 10.1007/s11262-019-01690-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 07/19/2019] [Indexed: 10/26/2022]
Abstract
Hepatitis B virus (HBV) exhibits a high degree of heterogeneity with at least 10 genotypes (A-J) identified to date. Intergenotypic recombination is relatively common. Previously, we investigated HBV drug resistance in HIV/HBV co-infected individuals in Ghana. After identifying multiple circulating genotypes and a novel D/E recombinant, we sought to determine if additional individuals were also infected with recombinant HBV. Partial genome sequences from three individuals were initially identified as genotype A4. Full-length HBV genomes were obtained using rolling circle amplification followed by PCR and shown to cluster with known A/E recombinant viruses. Similar recombination breakpoints were observed in these three individuals suggesting local spread of this novel recombinant HBV in Ghana.
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Affiliation(s)
- Ceejay L Boyce
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Stephaney Willis
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Timothy N A Archampong
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana
- Korle-Bu Teaching Hospital, Accra, Ghana
| | - Margaret Lartey
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana
- Korle-Bu Teaching Hospital, Accra, Ghana
| | - Kwamena W Sagoe
- Department of Medical Microbiology, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Adjoa Obo-Akwa
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Ernest Kenu
- Korle-Bu Teaching Hospital, Accra, Ghana
- School of Public Health, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Awewura Kwara
- Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, FL, USA
| | - Jason T Blackard
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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14
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Matlou MK, Gaelejwe LR, Musyoki AM, Rakgole JN, Selabe SG, Amponsah-Dacosta E. A novel hepatitis B virus recombinant genotype D4/E identified in a South African population. Heliyon 2019; 5:e01477. [PMID: 31008405 PMCID: PMC6453802 DOI: 10.1016/j.heliyon.2019.e01477] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 03/08/2019] [Accepted: 04/01/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Genetic diversity is a characteristic trait of the hepatitis B virus (HBV) and has been associated with different clinical outcomes. In South Africa, HBV infection is a major public health concern. Most HBV infections are caused by genotype A strains. However rare cases of infection with HBV genotype D have been reported. The purpose of this study was to investigate the molecular characteristics of a rare HBV subgenotype D4 isolate. METHODS The full-length genome of isolate ZADGM6964 was amplified in a one-step polymerase chain reaction. The amplified product was purified and cloned into a pGEM®-T Easy Vector System to investigate the genetic diversity of the viral quasi-populations. The primary isolate and clones were then directly sequenced and analysed using an array of bioinformatics software. RESULTS Phylogenetic analysis showed that the primary isolate and cloned sequences formed a monophyletic cluster away from subgenotype D4 reference strains. Further recombination analysis revealed that isolate ZADGM6964 was in fact a D4/E recombinant strain with breakpoints identified within the X and overlapping pre-Core/Core open reading frames with a >70% bootstrap confidence level. The recombinant genotype D4/E was found to be unique from other D/E strains archived in the genetic database, GenBank. CONCLUSION This study represents the first ever report on the isolation and molecular characterization of an HBV D4/E recombinant strain in South Africa. The findings provide evidence of further HBV genetic diversity in South Africa than has been previously reported.
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Affiliation(s)
- Mmatsatsi K. Matlou
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Lucinda R. Gaelejwe
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Andrew M. Musyoki
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
- Department of Microbiological Pathology, Sefako Makgatho Health Sciences University, Pretoria, South Africa
| | - J. Nare Rakgole
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Selokela G. Selabe
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
| | - Edina Amponsah-Dacosta
- HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Services, Pretoria, South Africa
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15
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McNaughton AL, D'Arienzo V, Ansari MA, Lumley SF, Littlejohn M, Revill P, McKeating JA, Matthews PC. Insights From Deep Sequencing of the HBV Genome-Unique, Tiny, and Misunderstood. Gastroenterology 2019; 156:384-399. [PMID: 30268787 PMCID: PMC6347571 DOI: 10.1053/j.gastro.2018.07.058] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 06/27/2018] [Accepted: 07/23/2018] [Indexed: 12/13/2022]
Abstract
Hepatitis B virus (HBV) is a unique, tiny, partially double-stranded, reverse-transcribing DNA virus with proteins encoded by multiple overlapping reading frames. The substitution rate is surprisingly high for a DNA virus, but lower than that of other reverse transcribing organisms. More than 260 million people worldwide have chronic HBV infection, which causes 0.8 million deaths a year. Because of the high burden of disease, international health agencies have set the goal of eliminating HBV infection by 2030. Nonetheless, the intriguing HBV genome has not been well characterized. We summarize data on the HBV genome structure and replication cycle, explain and quantify diversity within and among infected individuals, and discuss advances that can be offered by application of next-generation sequencing technology. In-depth HBV genome analyses could increase our understanding of disease pathogenesis and allow us to better predict patient outcomes, optimize treatment, and develop new therapeutics.
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Affiliation(s)
- Anna L McNaughton
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford, United Kingdom
| | - Valentina D'Arienzo
- Nuffield Department of Medicine, NDM Research Building, Oxford, United Kingdom
| | - M Azim Ansari
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford, United Kingdom
| | - Sheila F Lumley
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford, United Kingdom; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom
| | - Margaret Littlejohn
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, Australia; Department of Microbiology and Immunology, University of Melbourne. Melbourne, Australia
| | - Peter Revill
- Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, Australia; Department of Microbiology and Immunology, University of Melbourne. Melbourne, Australia
| | - Jane A McKeating
- Nuffield Department of Medicine, NDM Research Building, Oxford, United Kingdom
| | - Philippa C Matthews
- Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, Oxford, United Kingdom; Department of Infectious Diseases and Microbiology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom.
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16
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Assih M, Ouattara AK, Diarra B, Yonli AT, Compaore TR, Obiri-Yeboah D, Djigma FW, Karou S, Simpore J. Genetic diversity of hepatitis viruses in West-African countries from 1996 to 2018. World J Hepatol 2018; 10:807-821. [PMID: 30533182 PMCID: PMC6280160 DOI: 10.4254/wjh.v10.i11.807] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 09/10/2018] [Accepted: 10/23/2018] [Indexed: 02/06/2023] Open
Abstract
The severity of hepatic pathology and the response to treatment depend on the hepatitis virus genotype in the infected host. The objective of this review was to determine the distribution of hepatitis virus genotypes in West African countries. A systematic review of the literature in PubMed, Google Scholar and Science Direct was performed to identify 52 relevant articles reporting hepatitis A, B, C, D, E and G viruses genotypes. Hepatitis B virus (HBV) genotype E with a prevalence of 90.6% (95%CI: 0.891-0.920) found in this review, is characterized by low genetic diversity. Hepatitis C virus (HCV) genotypes 1 and 2 represented 96.4% of HCV infections in West African countries, while hepatitis delta virus, hepatitis A virus, hepatitis G virus genotypes 1 and HEV genotype 3 were reported in some studies in Ghana and Nigeria. HBV genotype E is characterized by high prevalence, low genetic diversity and wide geographical distribution. Further studies on the clinical implications of HBV genotype E and HCV genotypes 1 and 2 are needed for the development of an effective treatment against this viral hepatitis in West African countries. Surveillance of the distribution of different genotypes is also needed to reduce recombination rates and prevent the emergence of more virulent viral strains.
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Affiliation(s)
- Maléki Assih
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Abdoul Karim Ouattara
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso.
| | - Birama Diarra
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Albert Theophane Yonli
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Tegwindé Rebeca Compaore
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Dorcas Obiri-Yeboah
- Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Cape Coast 00233, Ghana
| | - Florencia Wendkuuni Djigma
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
| | - Simplice Karou
- Ecole Supérieure des Techniques Biologiques et Alimentaires (ESTBA-UL), Universite de Lome, Lome 00229, Togo
| | - Jacques Simpore
- Biochemistry-Microbiology, CERBA/LABIOGENE, Ouagadougou 02006, Burkina Faso
- Laboratory of Molecular Biology and Molecular Genetics (LABIOGENE) UFR/SVT, University Ouaga I Prof Joseph KI-ZERBO, Ouagadougou 00226, Burkina Faso
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17
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Gourari S, Brichler S, Le Gal F, Abdou-Chekaraou M, Beloufa MA, Khelifa R, Djaballah H, Boufekane M, Nani A, Afredj N, Debzi N, Dény P, Gordien E, Tazir M. Hepatitis B virus and hepatitis delta virus subtypes circulating in Algeria and seroprevalence of HDV infection. J Med Virol 2018; 91:72-80. [PMID: 30168584 DOI: 10.1002/jmv.25301] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2017] [Accepted: 06/15/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Little is known about molecular characteristics of HBV strains circulating in Algeria and there are few data regarding HDV infection. OBJECTIVES The aim of this study is to describe the genetic diversity of HBV and HDV strains existing in Algeria and to determine the seroprevalence of HDV infection. STUDY DESIGN Plasma samples from 134 patients were analyzed by enzyme immunoassay method for HBV and HDV serological markers. Genotyping of HBV and HDV strains were performed using direct sequencing followed by phylogenetic analyses of the PreS1 and R0 region of the HBV and HDV genome respectively. RESULTS The PreS1 gene was successfully amplified in 119 patients (82 males and 37 females). Phylogenetic analysis of HBV strains revealed the presence of genotypes D (86.5%) and A2 (11.76%). The subgenotypes D are distributed as follows: HBV/D7 (43.5%), HBV/D3 (24.75%), HBV/D1 (16.8%) and HBV/D2 (14.85%). A recombinant between genotypes A, E and D was found. The seroprevalence of HDV infection among HBV carriers was less than 5.35%. Only one isolate of HDV genotype 1 was identified. CONCLUSIONS Our data indicate the predominance of HBV subgenotype D7 and a low prevalence of HDV infection.
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Affiliation(s)
- Samir Gourari
- Service de Microbiologie, CHU Mustapha, Algiers, Algeria
| | - Ségolène Brichler
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | - Frédéric Le Gal
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | - Mariama Abdou-Chekaraou
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | | | - Rim Khelifa
- Service de Microbiologie, CHU Mustapha, Algiers, Algeria
| | | | | | | | - Nawel Afredj
- Service d'Hépatologie, CHU Mustapha, Algiers, Algeria
| | - Nabil Debzi
- Service d'Hépatologie, CHU Mustapha, Algiers, Algeria
| | - Paul Dény
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | - Emmanuel Gordien
- Service de Bactériologie, Virologie-Hygiène, Laboratoire associé au Centre National de Référence des Hépatites B, C et delta, Hôpital Avicenne, Bobigny, France
| | - Mohamed Tazir
- Service de Microbiologie, CHU Mustapha, Algiers, Algeria
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18
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Kostaki EG, Karamitros T, Stefanou G, Mamais I, Angelis K, Hatzakis A, Kramvis A, Paraskevis D. Unravelling the history of hepatitis B virus genotypes A and D infection using a full-genome phylogenetic and phylogeographic approach. eLife 2018; 7:36709. [PMID: 30082021 PMCID: PMC6118819 DOI: 10.7554/elife.36709] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 07/28/2018] [Indexed: 12/17/2022] Open
Abstract
Hepatitis B virus (HBV) infection constitutes a global public health problem. In order to establish how HBV was disseminated across different geographic regions, we estimated the levels of regional clustering for genotypes D and A. We used 916 HBV-D and 493 HBV-A full-length sequences to reconstruct their global phylogeny. Phylogeographic analysis was conducted by the reconstruction of ancestral states using the criterion of parsimony. The putative origin of genotype D was in North Africa/Middle East. HBV-D sequences form low levels of regional clustering for the Middle East and Southern Europe. In contrast, HBV-A sequences form two major clusters, the first including sequences mostly from sub-Saharan Africa, and the second including sequences mostly from Western and Central Europe. Conclusion: We observed considerable differences in the global dissemination patterns of HBV-D and HBV-A and different levels of monophyletic clustering in relation to the regions of prevalence of each genotype.
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Affiliation(s)
- Evangelia-Georgia Kostaki
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
| | - Timokratis Karamitros
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
- Department of ZoologyUniversity of OxfordOxfordUnited Kingdom
| | - Garyfallia Stefanou
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
| | - Ioannis Mamais
- Department of Health Sciences, School of SciencesEuropean University of CyprusNicosiaCyprus
| | - Konstantinos Angelis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
| | - Angelos Hatzakis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
| | - Anna Kramvis
- Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, Faculty of Health ScienceUniversity of the WitwatersrandJohannesburgSouth Africa
| | - Dimitrios Paraskevis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical SchoolNational and Kapodistrian University of AthensAthensGreece
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Bannister EG, Yuen L, Littlejohn M, Edwards R, Sozzi V, Colledge D, Li X, Locarnini S, Hardikar W, Revill PA. Molecular characterization of hepatitis B virus (HBV) in African children living in Australia identifies genotypes and variants associated with poor clinical outcome. J Gen Virol 2018; 99:1103-1114. [PMID: 29932395 DOI: 10.1099/jgv.0.001086] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Migration from sub-Saharan Africa is contributing to the rising incidence of chronic hepatitis B (CHB) infection and its complications in Australia. African CHB is associated with unique genotypes, such as E and A1, which are associated with reduced vaccine efficacy and early-onset hepatocellular carcinoma, respectively, although the prevalence of these genotypes outside Africa is poorly described. Treatment-naïve children of African origin with CHB were recruited at the Royal Children's Hospital Melbourne. Population-based sequencing of the complete HBV genome, or the clinically relevant basal core promoter (BCP)/precore (PC) region, was performed, and the HBV genotype/subgenotype assigned by phylogenetic analysis. HBV was characterized in serum from 67 children, median age 12.5 years. HBV genotype E was most frequent (70 %), with genotype D [25 %; subgenotypes D6 (formerly D7)/D3/D2)] and subgenotype A1 (5 %) also being identified. Despite their young age, over 50 % of the children were HBeAg-negative and had seroconverted to anti-HBe, with this being associated with canonical BCP/PC mutations in the majority of cases. The profile of HBV in African children living in Australia was characterized by early HBeAg seroconversion and infection with HBV variants associated with poor clinical outcome, as well as genotypes previously associated with reduced vaccine efficacy or rapid progression to liver cancer. These findings have important ramifications for patient monitoring and treatment guidelines in the Australian paediatric setting.
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Affiliation(s)
- Elizabeth G Bannister
- 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia.,2Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Victoria, Australia.,3Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
| | - Lilly Yuen
- 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
| | - Margaret Littlejohn
- 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
| | - Rosalind Edwards
- 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
| | - Vitina Sozzi
- 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
| | - Danni Colledge
- 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
| | - Xin Li
- 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
| | - Stephen Locarnini
- 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia
| | - Winita Hardikar
- 2Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Parkville, Victoria, Australia.,3Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
| | - Peter A Revill
- 1Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute of Infection and Immunity, Melbourne, 3000 Victoria, Australia.,4Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
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20
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Komas NP, Ghosh S, Abdou-Chekaraou M, Pradat P, Al Hawajri N, Manirakiza A, Laghoe GL, Bekondi C, Brichler S, Ouavéné JO, Sépou A, Yambiyo BM, Gody JC, Fikouma V, Gerber A, Abeywickrama Samarakoon N, Alfaiate D, Scholtès C, Martel N, Le Gal F, Lo Pinto H, Amri I, Hantz O, Durantel D, Lesbordes JL, Gordien E, Merle P, Drugan T, Trépo C, Zoulim F, Cortay JC, Kay AC, Dény P. Hepatitis B and hepatitis D virus infections in the Central African Republic, twenty-five years after a fulminant hepatitis outbreak, indicate continuing spread in asymptomatic young adults. PLoS Negl Trop Dis 2018; 12:e0006377. [PMID: 29698488 PMCID: PMC5940242 DOI: 10.1371/journal.pntd.0006377] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Revised: 05/08/2018] [Accepted: 03/08/2018] [Indexed: 12/13/2022] Open
Abstract
Hepatitis delta virus (HDV) increases morbidity in Hepatitis B virus (HBV)-infected patients. In the mid-eighties, an outbreak of HDV fulminant hepatitis (FH) in the Central African Republic (CAR) killed 88% of patients hospitalized in Bangui. We evaluated infections with HBV and HDV among students and pregnant women, 25 years after the fulminant hepatitis (FH) outbreak to determine (i) the prevalence of HBV and HDV infection in this population, (ii) the clinical risk factors for HBV and/or HDV infections, and (iii) to characterize and compare the strains from the FH outbreak in the 1980s to the 2010 HBV–HDV strains. We performed a cross sectional study with historical comparison on FH-stored samples (n = 179) from 159 patients and dried blood-spots from volunteer students and pregnant women groups (n = 2172). We analyzed risk factors potentially associated with HBV and HDV. Previous HBV infection (presence of anti-HBc) occurred in 345/1290 students (26.7%) and 186/870 pregnant women (21.4%)(p = 0.005), including 110 students (8.8%) and 71 pregnant women (8.2%), who were also HBsAg-positive (p = 0.824). HDV infection occurred more frequently in pregnant women (n = 13; 18.8%) than students (n = 6; 5.4%) (p = 0.010). Infection in childhood was probably the main HBV risk factor. The risk factors for HDV infection were age (p = 0.040), transfusion (p = 0.039), and a tendency for tattooing (p = 0.055) and absence of condom use (p = 0.049). HBV-E and HDV-1 were highly prevalent during both the FH outbreak and the 2010 screening project. For historical samples, due to storage conditions and despite several attempts, we could only obtain partial HDV amplification representing 25% of the full-length genome. The HDV-1 mid-eighties FH-strains did not form a specific clade and were affiliated to two different HDV-1 African subgenotypes, one of which also includes the 2010 HDV-1 strains. In the Central African Republic, these findings indicate a high prevalence of previous and current HBV-E and HDV-1 infections both in the mid-eighties fulminant hepatitis outbreak and among asymptomatic young adults in 2010, and reinforce the need for universal HBV vaccination and the prevention of HDV transmission among HBsAg-positive patients through blood or sexual routes. In the Central African Republic (CAR), due to 20 years of conflict, the health system has been disorganized. This could contribute to maintenance of high transmission levels of Hepatitis B Virus (HBV) and its satellite Hepatitis Delta Virus (HDV). This work studies the evolution of both infections 25 years after a fulminant hepatitis (FH) outbreak occurring in the mid-1980s associated with HDV superinfection. In young asymptomatic adults, the results show that both HBV and HDV were still actively circulating in CAR in 2010. Indeed, more than one third of HBV-infected individuals were chronic HBV carriers. Furthermore, HDV infection could be spreading among 10% of them through blood and sexual transmission. The past FH outbreak and contemporary infections were both associated with heterogeneous HDV-1 strains, combined with HBV-E. Vaccination against HBV was uncommon among pregnant women and students, even among medical students. The study constitutes warning signals to help CAR health-care reconstruction and underlines the importance of HBV vaccination. The high level of HBV infection creates a background for HDV superinfection. Neonatal HBV vaccination is needed, together with vaccination of unprotected populations. Awareness of health authorities as well as the general public would help reduce HBV and HDV infections.
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Affiliation(s)
- Narcisse Patrice Komas
- Laboratoire des hépatites virales, Institut Pasteur de Bangui, Bangui, Central African Republic
- * E-mail: (NPK); (PD)
| | - Sumantra Ghosh
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Mariama Abdou-Chekaraou
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
- Service de Microbiologie Clinique, Hôpital Avicenne, Groupe des Hôpitaux Universitaires Paris Seine Saint-Denis, Assistance Publique–Hôpitaux de Paris, Bobigny, France, Université Paris 13/Sorbonne Paris Cité, UFR Santé Médecine Biologie Humaine, Bobigny, France
| | - Pierre Pradat
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
- Center for Clinical Research, Croix-Rousse Hospital, Lyon, France
- Hospices Civils de Lyon, Lyon, France/Université de Lyon I, Lyon, France
| | | | - Alexandre Manirakiza
- Service d’Épidémiologie, Institut Pasteur de Bangui, Bangui, Central African Republic
| | - Gina Laure Laghoe
- Laboratoire des hépatites virales, Institut Pasteur de Bangui, Bangui, Central African Republic
| | - Claudine Bekondi
- Laboratoire des hépatites virales, Institut Pasteur de Bangui, Bangui, Central African Republic
| | - Ségolène Brichler
- Service de Microbiologie Clinique, Hôpital Avicenne, Groupe des Hôpitaux Universitaires Paris Seine Saint-Denis, Assistance Publique–Hôpitaux de Paris, Bobigny, France, Université Paris 13/Sorbonne Paris Cité, UFR Santé Médecine Biologie Humaine, Bobigny, France
| | - Jean-Omer Ouavéné
- Service de Médecine Interne, Hôpital de l’Amitié, Avenue Indépendance, Bangui, Central African Republic
| | - Abdoulaye Sépou
- Service de Gynécologie Obstétrique, Hôpital Communautaire de Bangui, Avenue des Martyrs, Bangui, Central African Republic
| | - Brice Martial Yambiyo
- Service d’Épidémiologie, Institut Pasteur de Bangui, Bangui, Central African Republic
| | | | - Valentin Fikouma
- Centre de Traitement Ambulatoire de l’Hôpital Communautaire de Bangui, Bangui, Central African Republic
| | - Athénais Gerber
- Service de Microbiologie Clinique, Hôpital Avicenne, Groupe des Hôpitaux Universitaires Paris Seine Saint-Denis, Assistance Publique–Hôpitaux de Paris, Bobigny, France, Université Paris 13/Sorbonne Paris Cité, UFR Santé Médecine Biologie Humaine, Bobigny, France
| | | | - Dulce Alfaiate
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Caroline Scholtès
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
- Hospices Civils de Lyon, Lyon, France/Université de Lyon I, Lyon, France
- Laboratoire de Virologie, Croix-Rousse Hospital, Lyon, France
| | - Nora Martel
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Frédéric Le Gal
- Service de Microbiologie Clinique, Hôpital Avicenne, Groupe des Hôpitaux Universitaires Paris Seine Saint-Denis, Assistance Publique–Hôpitaux de Paris, Bobigny, France, Université Paris 13/Sorbonne Paris Cité, UFR Santé Médecine Biologie Humaine, Bobigny, France
| | - Hugo Lo Pinto
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Ikram Amri
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Olivier Hantz
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - David Durantel
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Jean-Louis Lesbordes
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Emmanuel Gordien
- Service de Microbiologie Clinique, Hôpital Avicenne, Groupe des Hôpitaux Universitaires Paris Seine Saint-Denis, Assistance Publique–Hôpitaux de Paris, Bobigny, France, Université Paris 13/Sorbonne Paris Cité, UFR Santé Médecine Biologie Humaine, Bobigny, France
| | - Philippe Merle
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
- Hospices Civils de Lyon, Lyon, France/Université de Lyon I, Lyon, France
| | - Tudor Drugan
- Department of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Christian Trépo
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
- Hospices Civils de Lyon, Lyon, France/Université de Lyon I, Lyon, France
| | - Fabien Zoulim
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
- Hospices Civils de Lyon, Lyon, France/Université de Lyon I, Lyon, France
| | - Jean-Claude Cortay
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Alan Campbell Kay
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
| | - Paul Dény
- INSERM, U1052, UMR CNRS 5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
- Service de Microbiologie Clinique, Hôpital Avicenne, Groupe des Hôpitaux Universitaires Paris Seine Saint-Denis, Assistance Publique–Hôpitaux de Paris, Bobigny, France, Université Paris 13/Sorbonne Paris Cité, UFR Santé Médecine Biologie Humaine, Bobigny, France
- * E-mail: (NPK); (PD)
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21
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Molecular characterization of the full-length genome sequences of HDV strains circulating in Tunisia. Arch Virol 2018. [PMID: 29516244 DOI: 10.1007/s00705-018-3790-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
While Tunisia is endemic for hepatitis B virus (HBV), a recent large-scale retrospective study, revealed a very low prevalence (2%) of hepatitis Delta virus (HDV) (Yacoubi et al. in J Clin Virol 72:126-132, 2015). All strains were classified within the genotype 1 (HDV-1) as assessed by nucleotide sequencing of the so-called 'R0' region of the genome described previously. In this study, we aimed to determine the full-length genome sequence of HDV isolates in order to fully characterize the HDV strains spreading in Tunisia. Eleven HDV antibody and RNA positive samples were obtained from the 1615 clinical samples previously studied. The whole genome sequence was obtained for 5 strains by sequencing and realignment of four overlapping regions covering the entire genome, followed by extensive phylogenetic analyses. Tunisian sequences segregated together with Turkish and African sequences and showed 60% GC content. Alignment with an HDV-1 consensus sequence revealed that they exhibited several point mutations in different functional domains of the delta proteins that, according to previous studies, might possibly affect their properties. In conclusion, the first full-length genome sequences of Tunisian HDV isolates are provided, isolates which are closely related to Turkish and Sub-Saharan Africa strains, supporting the hypothesis for the spread of HDV-1-strains from Africa via Tunisia to Turkey, before spread to the rest of the world.
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22
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Boyce CL, Ganova-Raeva L, Archampong TNA, Lartey M, Sagoe KW, Obo-Akwa A, Kenu E, Kwara A, Blackard JT. Identification and comparative analysis of hepatitis B virus genotype D/E recombinants in Africa. Virus Genes 2017; 53:538-547. [PMID: 28567562 PMCID: PMC5710801 DOI: 10.1007/s11262-017-1469-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 05/25/2017] [Indexed: 12/17/2022]
Abstract
Globally, there are approximately 240 million people chronically infected with hepatitis B virus (HBV)-a major cause of hepatocellular carcinoma. Ten different HBV genotypes (A-J) have been identified with distinct geographic distributions. Novel variants generated by recombination between different HBV genotypes have been documented worldwide and represent an important element of genetic variability with possible clinical implications. Here, the complete genome sequence of an HBV genotype D/E recombinant from Ghana is reported. The full-length sequence was obtained using rolling circle amplification followed by PCR and sequenced using next-generation sequencing (NGS). A consensus sequence was extracted from the NGS data and underwent phylogenetic analysis to determine genotype, as well as the recombination pattern. Subsequently, the sequence was compared to recombinants described previously in Africa. Based on MCMC phylogenetic analysis, SimPlot recombination analyses, and intragroup genetic distance, the isolate 007N full-length genome is unique compared to other reported D/E recombinants in Africa.
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Affiliation(s)
- Ceejay L Boyce
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Lilia Ganova-Raeva
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Timothy N A Archampong
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana
- Korle-Bu Teaching Hospital, Accra, Ghana
| | - Margaret Lartey
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana
- Korle-Bu Teaching Hospital, Accra, Ghana
| | - Kwamena W Sagoe
- Department of Medical Microbiology, School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Adjoa Obo-Akwa
- Department of Medicine and Therapeutics, School of Medicine and Dentistry, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Ernest Kenu
- Korle-Bu Teaching Hospital, Accra, Ghana
- School of Public Health, College of Health Sciences, University of Ghana, Accra, Ghana
| | - Awewura Kwara
- Warren Alpert Medical School of Brown University, Providence, RI, USA
- The Miriam Hospital, Providence, RI, USA
- Division of Infectious Diseases and Global Medicine, University of Florida, Gainesville, FL, USA
| | - Jason T Blackard
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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Liu T, Wang F, Zhang S, Wang F, Meng Q, Zhang G, Cui F, Dunzhu D, Yin W, Bi S, Shen L. Whole-gene analysis of two groups of hepatitis B virus C/D inter-genotype recombinant strains isolated in Tibet, China. PLoS One 2017; 12:e0179846. [PMID: 28654691 PMCID: PMC5487078 DOI: 10.1371/journal.pone.0179846] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2016] [Accepted: 06/05/2017] [Indexed: 12/21/2022] Open
Abstract
Tibet is a highly hepatitis B virus (HBV) endemic area. Two types of C/D recombinant HBV are commonly isolated in Tibet and have been previously described. In an effort to better understand the molecular characteristic of these C/D recombinant strains from Tibet, we undertook a multistage random sampling project to collect HBsAg positive samples. Molecular epidemiological and bio-informational technologies were used to analyze the characteristics of the sequences found in this study. There were 60 samples enrolled in the survey, and we obtained 19 whole-genome sequences. 19 samples were all C/D recombinant, and could be divided into two sub-types named C/D1 and C/D2 according to the differences in the location of the recombinant breakpoint. The recombination breakpoint of the 10 strains belonging to the C/D1 sub-type was located at nt750, while the 9 stains belonging to C/D2 had their recombination break point at nt1530. According to whole-genome sequence analysis, the 19 identified strains belong to genotype C, but the nucleotide distance was more than 5% between the 19 strains and sub-genotypes C1 to C15. The distance between C/D1with C2 was 5.8±2.1%, while the distance between C/D2 with C2 was 6.4±2.1%. The parental strain was most likely sub-genotype C2. C/D1 strains were all collected in the middle and northern areas of Tibet including Lhasa, Linzhi and Ali, while C/D2 was predominant in Shannan in southern Tibet. This indicates that the two recombinant genotypes are regionally distributed in Tibet. These results provide important information for the study of special HBV recombination events, gene features, virus evolution, and the control and prevention policy of HBV in Tibet.
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Affiliation(s)
- Tiezhu Liu
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Fuzhen Wang
- National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Shuang Zhang
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Feng Wang
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Qingling Meng
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Guomin Zhang
- National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Fuqiang Cui
- National Immunization Program, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Dorji Dunzhu
- Tibetan Center for Disease Control and Prevention, Lhasa, Tibet, China
| | - Wenjiao Yin
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Shengli Bi
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Liping Shen
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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Fujiwara K, Matsunami K, Iio E, Nojiri S, Joh T. Novel non-canonical genetic rearrangements termed "complex structural variations" in HBV genome. Virus Res 2017; 238:84-93. [PMID: 28627394 DOI: 10.1016/j.virusres.2017.06.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 06/11/2017] [Accepted: 06/12/2017] [Indexed: 01/05/2023]
Abstract
BACKGROUNDS AND AIMS Chronic hepatitis B virus (HBV) infection is an important worldwide public health issue. Further knowledge on the characteristics of HBV will facilitate its eradication. Genome structural variations (SVs) are defined by its canonical form such as duplication, deletion, and insertion. However, recent studies have reported complex SVs that cannot be explained by those canonical SVs. A HBV strain (UK2) with an unusual genome structure rearrangement that was completely different from known mutations or rearrangements was previously reported. Thus, this study was conducted to confirm the rearrangement in UK2 as a novel complex SV, and to find additional HBV strains with complex SVs. Further, the contribution of complex SVs in hepadnavirus variability was investigated. METHODS The genome rearrangement pattern in UK2 was analyzed. Further, a search of online databases retrieved additional HBV strains which were candidates to harbor complex SVs. The architecture of each rearrangement in the candidate strains was analyzed by bioinformatical tools. In addition, alignment of woolly monkey hepatitis virus (WMHV) and HBV from human and non-human primates was performed to investigate the contribution of complex SVs to variability of hepadnavirus. RESULTS The rearrangement in UK2 was confirmed as a complex SV. An additional 15 HBV strains were retrieved from databases, and confirmed as harboring complex SVs. Complex combinations of deletion, insertion, and duplication characterized the novel rearrangements. The complex SVs in six strains (37.5%) were composed of deletion, insertion, and duplication. The complex SVs in another six strains (37.5%) consisted of deletion and insertion, followed by insertions and duplication in three strains (18.8%), and deletion and duplication in one strain (6.3%). In addition, unique preS1 promoter insertions, which contained the hepatocyte nuclear factor 1 binding site, were observed in seven (43.8%) of 16 strains. Further, analysis of the genetic sequences of WMHV and HBV from human and non-human primates showed that complex combinations of deletions and insertions accounted for their genetic differences. CONCLUSIONS Non-canonical genetic rearrangements termed complex SVs were observed in HBV. Further, complex SVs accounted for the genetic differences of WMHV and HBV from human and non-human primates.
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Affiliation(s)
- Kei Fujiwara
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
| | - Kayoko Matsunami
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Etsuko Iio
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Shunsuke Nojiri
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Takashi Joh
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Lawson-Ananissoh LM, Attia KA, Diallo D, Doffou S, Kissi YH, Bangoura D, Kouamé D, Mahassadi KA, Yao-Bathaix F, Yoman TN. Distribution et implications cliniques des génotypes du virus de l’hépatite B chez 33 porteurs chroniques du virus de l’hépatite B en Côte-d’Ivoire. ACTA ACUST UNITED AC 2017. [DOI: 10.1007/s12157-017-0726-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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26
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Hundie GB, Stalin Raj V, Gebre Michael D, Pas SD, Koopmans MP, Osterhaus ADME, Smits SL, Haagmans BL. A novel hepatitis B virus subgenotype D10 circulating in Ethiopia. J Viral Hepat 2017; 24:163-173. [PMID: 27808472 DOI: 10.1111/jvh.12631] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 10/06/2016] [Indexed: 12/13/2022]
Abstract
Hepatitis B virus (HBV) is genetically highly divergent and classified in ten genotypes and forty subgenotypes in distinct ethno-geographic populations worldwide. Ethiopia is a country with high HBV prevalence; however, little is known about the genetic variability of HBV strains that circulate. Here, we characterize the complete genome of 29 HBV strains originating from five Ethiopian regions, by 454 deep sequencing and Sanger sequencing. Phylogenetically, ten strains were classified as genotype A1 and nineteen as genotype D. Fifteen genotype D strains, provisionally named subgenotype D10, showed a novel distinct cluster supported by high bootstrap value and >4% nucleotide divergence from other known subgenotypes. In addition, the novel D10 strains harboured nine unique amino acid signatures in the surface, polymerase and X genes. Seventy-two per cent of the genotype D strains had the precore premature stop codon G1896A. In addition, 63% genotype A and 33% genotype D strains had the basal core promoter mutations, A1762T/G1764A. Furthermore, four pre-S deletion variants and two recombinants were identified in this study. In conclusion, we identified a novel HBV subgenotype D10 circulating in Ethiopia, underlining the high genetic variability of HBV strains in Africa.
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Affiliation(s)
- G B Hundie
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | - V Stalin Raj
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | - D Gebre Michael
- National blood bank services, Ministry of Health, Addis Ababa, Ethiopia
| | - S D Pas
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | - M P Koopmans
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
| | - A D M E Osterhaus
- Artemis One health, Utrecht, The Netherlands.,Center for Infection Medicine and Zoonoses Research, University of Veterinary Medicine, Hannover, Germany
| | - S L Smits
- ViroClinics BioScience BV, Rotterdam, The Netherlands
| | - B L Haagmans
- Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands
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27
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Thurnheer MC, Edwards R, Schulz TR, Yuen L, Littlejohn M, Revill P, Bannister E, Chu M, Tanyeri F, Wade A, Biggs BA, Sasadeusz J. Genotypic profiles of hepatitis B in African immigrants and their clinical relevance. J Med Virol 2016; 89:1000-1007. [PMID: 27862013 DOI: 10.1002/jmv.24732] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 10/24/2016] [Accepted: 11/09/2016] [Indexed: 01/05/2023]
Abstract
Hepatitis B virus (HBV) from 40 adult African immigrants in Australia was characterized to determine the prevalence of different HBV genotypes and subgenotypes. A mutational analysis was then performed to determine the presence of clinically significant mutations and correlate them to clinical outcomes. Initial sequencing analysis revealed 13 with genotype A (32.5%), 13 with genotype D (32.5%), and 14 with genotype E (35%). Serology showed that 37 were HBeAg negative. Phylogenetic analysis identified a high prevalence (25%) of HBV subgenotype A1 in our cohort, a subgenotype which has been associated with more aggressive clinical disease. BCP/PC sequencing was obtained for 38 patients. BCP and/or PC mutations were identified in 36/38 (95%). The median viral load of all patients was 2995 IU/mL and most of the pathology results were within the normal range. Only one patient had an increased APRI score of 1.1 suggestive of cirrhosis. We present novel information on the HBV genotypes amongst the African population in Australia along with clinical correlates. The high prevalence of A1 subgenotype in this population supports the current Australian recommendation to commence hepatocellular carcinoma screening in Africans with chronic HBV from 20 years old.
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Affiliation(s)
- Maria Christine Thurnheer
- Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Doherty Institute, Melbourne, Victoria, 3000, Australia
| | - Rosalind Edwards
- Victorian Infectious Diseases Reference Laboratory, at the Doherty Institute, Melbourne, Victoria, 3000, Australia
| | - Thomas Ray Schulz
- Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Doherty Institute, Melbourne, Victoria, 3000, Australia.,Department of Medicine/ RMH, University of Melbourne, at the Doherty Institute, Melbourne, Victoria, 3000, Australia
| | - Lilly Yuen
- Victorian Infectious Diseases Reference Laboratory, at the Doherty Institute, Melbourne, Victoria, 3000, Australia
| | - Margaret Littlejohn
- Victorian Infectious Diseases Reference Laboratory, at the Doherty Institute, Melbourne, Victoria, 3000, Australia
| | - Peter Revill
- Victorian Infectious Diseases Reference Laboratory, at the Doherty Institute, Melbourne, Victoria, 3000, Australia
| | - Elizabeth Bannister
- Victorian Infectious Diseases Reference Laboratory, at the Doherty Institute, Melbourne, Victoria, 3000, Australia
| | - Melissa Chu
- Department of Medicine, University of Melbourne, Parkville, Victoria, 3050, Australia
| | - Firuz Tanyeri
- Department of Medicine, University of Melbourne, Parkville, Victoria, 3050, Australia
| | - Amanda Wade
- Department of Infectious Diseases, University Hospital, Geelong, Victoria, 3220, Australia
| | - Beverley-Ann Biggs
- Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Doherty Institute, Melbourne, Victoria, 3000, Australia.,Department of Medicine/ RMH, University of Melbourne, at the Doherty Institute, Melbourne, Victoria, 3000, Australia
| | - Joseph Sasadeusz
- Victorian Infectious Diseases Service, The Royal Melbourne Hospital, at the Doherty Institute, Melbourne, Victoria, 3000, Australia
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28
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Candotti D, Diarra B, Bisseye C, Tao I, Pham Quang K, Sanou M, Laperche S, Sanogo R, Allain JP, Simpore J. Molecular characterization of hepatitis B virus in blood donors from Burkina Faso: Prevalence of quasi-subgenotype A3, genotype E, and mixed infections. J Med Virol 2016; 88:2145-2156. [PMID: 27253483 DOI: 10.1002/jmv.24589] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2016] [Indexed: 12/16/2022]
Abstract
Burkina Faso is a highly endemic area for Hepatitis B virus (HBV) which remains a major challenge for blood safety with >13% of candidate blood donors being chronically infected. However, little is known about the molecular epidemiology of the viral strains currently circulating. In this study, 99 HBV strains from HBsAg positive candidate blood donors in Ougadougou were genetically characterized by sequencing the pre-S/S region of the viral genome. Phylogenetic analyses revealed a 25% prevalence of HBV quasi-subgenotype A3 (A3QS ) co-circulating with the confirmed dominant HBV genotype E (72%). HBV/A3QS sequences formed a sub-cluster closely related to West-African sequences previously characterized, and showed a low intra-group genetic diversity (0.75%) suggesting a relatively recent spreading of HBV/A3QS strains in Burkina Faso. Low genetic diversity of genotype E strains compared to A3QS was confirmed. Mixed infections with the two genotypes were identified in 3% of the donors tested and contributed to artifacts during PCR amplification of the viral genome leading to erroneous apparent intergenotype recombinant sequences. While the co-circulation of two HBV genotypes in a restricted area may favor the emergence of intergenotype recombinant variants, strictly controlled molecular experimental procedures should be used to accurately characterize HBV circulating recombinant forms. J. Med. Virol. 88:2145-2156, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Daniel Candotti
- INTS/National Institute of Blood Transfusion, Department of Blood-Transmitted Agents, National Reference Centre for Viral Hepatitis B&C and HIV in Transfusion, Paris, France. .,Department of Haematology, University of Cambridge, Cambridge, United Kingdom.
| | - Birama Diarra
- Biomolecular Research Centre Pietro Annigoni, LABIOGENE, University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Cyrille Bisseye
- Biomolecular Research Centre Pietro Annigoni, LABIOGENE, University of Ouagadougou, Ouagadougou, Burkina Faso.,Laboratory of Molecular and Cellular Biology, University of Sciences of Masuku, Franceville, Gabon
| | - Issoufou Tao
- Biomolecular Research Centre Pietro Annigoni, LABIOGENE, University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Kei Pham Quang
- INTS/National Institute of Blood Transfusion, Department of Blood-Transmitted Agents, National Reference Centre for Viral Hepatitis B&C and HIV in Transfusion, Paris, France
| | - Mahamoudou Sanou
- Unit of Formation in Health Sciences (UFR-SDS), University of Ouagadougou, Ouagadougou, Burkina Faso
| | - Syria Laperche
- INTS/National Institute of Blood Transfusion, Department of Blood-Transmitted Agents, National Reference Centre for Viral Hepatitis B&C and HIV in Transfusion, Paris, France
| | - Rokia Sanogo
- Faculty of Pharmacy, University of Engineering Sciences and Technology of Bamako, Bamako, Mali
| | - Jean-Pierre Allain
- Department of Haematology, University of Cambridge, Cambridge, United Kingdom
| | - Jacques Simpore
- Biomolecular Research Centre Pietro Annigoni, LABIOGENE, University of Ouagadougou, Ouagadougou, Burkina Faso
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29
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Tong S, Revill P. Overview of hepatitis B viral replication and genetic variability. J Hepatol 2016; 64:S4-S16. [PMID: 27084035 PMCID: PMC4834849 DOI: 10.1016/j.jhep.2016.01.027] [Citation(s) in RCA: 309] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Revised: 01/18/2016] [Accepted: 01/25/2016] [Indexed: 02/06/2023]
Abstract
Chronic infection with hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). HBV isolates worldwide can be divided into ten genotypes. Moreover, the immune clearance phase selects for mutations in different parts of the viral genome. The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype and adaptive mutations, as well as environmental factors. Core promoter mutations and mutations abolishing hepatitis B e antigen (HBeAg) expression have been implicated in acute liver failure, while genotypes B, C, subgenotype A1, core promoter mutations, preS deletions, C-terminal truncation of envelope proteins, and spliced pregenomic RNA are associated with HCC development. Our efforts to treat and prevent HBV infection are hampered by the emergence of drug resistant mutants and vaccine escape mutants. This paper provides an overview of the HBV life cycle, followed by review of HBV genotypes and mutants in terms of their biological properties and clinical significance.
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Affiliation(s)
- Shuping Tong
- Liver Research Center, Rhode Island Hospital, The Alpert Warren School of Medicine, Brown University, Providence, RI, USA; Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Peter Revill
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Doherty Institute, Melbourne, VIC, Australia ()
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30
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El Hadad S, Alakilli S, Rabah S, Sabir J. Sequence analysis of sub-genotype D hepatitis B surface antigens isolated from Jeddah, Saudi Arabia. Saudi J Biol Sci 2016; 25:838-847. [PMID: 29740253 PMCID: PMC5936882 DOI: 10.1016/j.sjbs.2016.03.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2015] [Revised: 02/16/2016] [Accepted: 03/05/2016] [Indexed: 12/20/2022] Open
Abstract
Little is known about the prevalence of HBV genotypes/sub-genotypes in Jeddah province, although the hepatitis B virus (HBV) was identified as the most predominant type of hepatitis in Saudi Arabia. To characterize HBV genotypes/sub-genotypes, serum samples from 15 patients with chronic HBV were collected and subjected to HBsAg gene amplification and sequence analysis. Phylogenetic analysis of the HBsAg gene sequences revealed that 11 (48%) isolates belonged to HBV/D while 4 (18%) were associated with HBV/C. Notably, a HBV/D sub-genotype phylogenetic tree identified that eight current isolates (72%) belonged to HBV/D1, whereas three isolates (28%) appeared to be more closely related to HBV/D5, although they formed a novel cluster supported by a branch with 99% bootstrap value. Isolates belonging to D1 were grouped in one branch and seemed to be more closely related to various strains isolated from different countries. For further determination of whether the three current isolates belonged to HBV/D5 or represented a novel sub-genotype, HBV/DA, whole HBV genome sequences would be required. In the present study, we verified that HBV/D1 is the most prevalent HBV sub-genotype in Jeddah, and identified novel variant mutations suggesting that an additional sub-genotype designated HBV/DA should be proposed. Overall, the results of the present HBsAg sequence analyses provide us with insights regarding the nucleotide differences between the present HBsAg/D isolates identified in the populace of Jeddah, Saudi Arabia and those previously isolated worldwide. Additional studies with large numbers of subjects in other areas might lead to the discovery of the specific HBV strain genotypes or even additional new sub-genotypes that are circulating in Saudi Arabia.
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Key Words
- C/pre C, HBV core/pre Core gene
- DDBJ, DNA Data Bank of Japan
- EMBL, European Molecular Biology Laboratory
- HAV, hepatitis A virus
- HBV sub-genotypes
- HBV, hepatitis B virus
- HBV/D
- HBsAg
- HBsAg, HBV surface antigen
- HCC, hepatocellular carcinoma
- HCV, hepatitis C virus
- Hepatitis B virus
- IFN, interferon
- P, HBV polymerase gene
- PCR, polymerase chain reaction
- Population studies
- Pre S1/Pre S2/S, HBsAg genes
- Viral isolates
- X, HBV X gene
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Affiliation(s)
- Sahar El Hadad
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Saleha Alakilli
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Samar Rabah
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Jamal Sabir
- Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
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31
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Ochwoto M, Kimotho JH, Oyugi J, Okoth F, Kioko H, Mining S, Budambula NLM, Giles E, Andonov A, Songok E, Osiowy C. Hepatitis B infection is highly prevalent among patients presenting with jaundice in Kenya. BMC Infect Dis 2016; 16:101. [PMID: 26932656 PMCID: PMC4774020 DOI: 10.1186/s12879-016-1409-2] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Accepted: 02/02/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Viral hepatitis is a major concern worldwide, with hepatitis A (HAV) and E (HEV) viruses showing sporadic outbreaks while hepatitis B (HBV) and C (HCV) viruses are associated with chronic hepatitis, cirrhosis and hepatocellular carcinoma. The present study determined the proportion, geographic distribution and molecular characterization of hepatitis viruses among patients seeking medical services at hospitals throughout Kenya. METHODS Patients presenting with jaundice at four selected hospitals were recruited (n = 389). Sera were tested for the presence of antibody to hepatitis viruses A through E, and HBV surface antigen (HBsAg). Nucleic acid from anti-HAV IgM antibody and HBsAg positive samples was extracted, amplified and sequenced. RESULTS Chronic HBV infection was the leading cause of morbidity among patients with symptoms of liver disease seeking medical help. Incident HCV, HEV and HDV infection were not detected among the patients in this study, while the proportion of acute HAV was low; HAV IgM positivity was observed in 6.3 % of patients and sequencing revealed that all cases belonged to genotype 1B. HCV seropositivity upon initial screening was 3.9 % but none were confirmed positive by a supplementary immunoblot assay. There was no serological evidence of HDV and acute HEV infection (anti-HEV IgM). HBsAg was found in 50.6 % of the patients and 2.3 % were positive for IgM antibody to the core protein, indicating probable acute infection. HBV genotype A was predominant (90.3 %) followed by D (9.7 %) among HBV DNA positive specimens. Full genome analysis showed HBV/D isolates having similarity to both D4 and D6 subgenotypes and D/E recombinant reference sequences. Two recombinant sequences demonstrated > 4 % nucleotide divergence from other previously known D/E recombinants. CONCLUSIONS HBV is highly prevalent among patients seeking care for symptoms consistent with hepatitis, compared to the general population. Molecular characterization of HBV isolates indicated recombinant strains that may give rise to new circulating variants. There is a need to document the prevalence, clinical manifestation and distribution of the variants observed. HAV genotype 1B, prevalent in Africa, was observed; however, the absence of HCV, HDV and acute HEV in this study does not rule out their presence in Kenya.
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Affiliation(s)
| | | | - Julius Oyugi
- Medical Microbiology Department, University of Nairobi, Nairobi, Kenya.
| | - Fredrick Okoth
- Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
| | | | - Simeon Mining
- Moi University and Moi Teaching and Referral Hospital, Eldoret, Kenya.
| | - Nancy L M Budambula
- Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya. .,Present address: Embu University College, Embu, Kenya.
| | - Elizabeth Giles
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
| | - Anton Andonov
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
| | - Elijah Songok
- Kenya Medical Research Institute (KEMRI), Nairobi, Kenya.
| | - Carla Osiowy
- National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
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32
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Brah S, Moussa S, Inoua A, Alhousseini DM, Daou M, Madougou B, Romera MH, Hamadou A, Adehossi E, Parola P, Colson P. Molecular characterization of hepatitis B virus from chronically-infected patients in Niamey, Niger. Int J Infect Dis 2016; 45:18-23. [PMID: 26899956 DOI: 10.1016/j.ijid.2016.02.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2015] [Revised: 02/08/2016] [Accepted: 02/10/2016] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES In Niger, 65% of hepatocarcinoma and 75% of cirrhosis cases were due to hepatitis B virus (HBV). We studied the genotypic characteristics of HBsAg in chronically HBV-infected patients in Niamey. METHODS We studied prospectively HBV genotypic patterns among hospitalized patients with HBV infection in the National Hospital of Niamey, Niger. Patients were screened for hepatitis B surface antigen (HBsAg) and HBV genotyping was performed on the HBsAg-positive patients. RESULTS In this study, we have confirmed the predominance of the HBV genotype E (HBV-E) in Niger and have identified 2 recombinant forms including HBV-E/D and HBV-A3/E reported previously among blood donors in Niger and Ghana, respectively. Amino acid substitutions found in HBV sequences obtained here included P120T, S143L, G145A and A194T. These substitutions were characterized as being associated with modified antigenicity and, notably, with impaired serological detection of HBsAg, while the A194T variant was found to have a controversial role in reduced susceptibility to tenofovir. CONCLUSIONS We have identified two recombinant HBV forms and rare genotypic patterns in Niger that may affect hepatitis B surface antigen antigenicity, and improve current knowledge of epidemiological, clinical and virological patterns of hepatitis B in this country.
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Affiliation(s)
- Souleymane Brah
- IHU Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Service de Maladies Infectieuses, Centre Hospitalo-Universitaire Nord, Assistance Publique - Hôpitaux de Marseille, chemin des Bourrely, 13915 Marseille cedex 20; Service de médecine interne, Hôpital National de Niamey, BP 238 - Niger
| | - Sahada Moussa
- Service de maladies infectieuses, Hôpital National de Niamey, BP 238 - Niger
| | - Achirou Inoua
- Service de médecine interne, Hôpital National de Niamey, BP 238 - Niger
| | | | - Mamane Daou
- Service de médecine interne, Hôpital National de Niamey, BP 238 - Niger
| | - Boubacar Madougou
- Service de gastro entérologie, Hôpital National de Niamey, BP 238 - Niger
| | - Marie-Hélène Romera
- IHU Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, 264 rue Saint-Pierre 13385, Marseille CEDEX 05, France
| | - Adamou Hamadou
- Service de médecine interne, Hôpital National de Niamey, BP 238 - Niger
| | - Eric Adehossi
- Service de médecine interne, Hôpital National de Niamey, BP 238 - Niger
| | - Philippe Parola
- IHU Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Service de Maladies Infectieuses, Centre Hospitalo-Universitaire Nord, Assistance Publique - Hôpitaux de Marseille, chemin des Bourrely, 13915 Marseille cedex 20; Aix-Marseille University, URMITE UM 63 CNRS 7278 IRD 198 INSERM U1905, 27 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France
| | - Philippe Colson
- Aix-Marseille University, URMITE UM 63 CNRS 7278 IRD 198 INSERM U1905, 27 boulevard Jean Moulin, 13385 Marseille CEDEX 05, France; IHU Méditerranée Infection, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Centre Hospitalo-Universitaire Timone, Assistance Publique-Hôpitaux de Marseille, 264 rue Saint-Pierre 13385, Marseille CEDEX 05, France.
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François-Souquière S, Makuwa M, Bisvigou U, Kazanji M. Epidemiological and molecular features of hepatitis B and hepatitis delta virus transmission in a remote rural community in central Africa. INFECTION GENETICS AND EVOLUTION 2015; 39:12-21. [PMID: 26747245 DOI: 10.1016/j.meegid.2015.12.021] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Revised: 12/21/2015] [Accepted: 12/29/2015] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) and hepatitis delta virus (HDV) occur worldwide and are prevalent in both urban and remote rural communities. In a remote village in Gabon, central Africa, we observed a high prevalence of HBsAg carriage and HDV infection, particularly in children and adolescents. The prevalence of HBsAg differed significantly by gender and age, females being more likely than males to carry the HBsAg during the first 10 years of life, while the prevalence was higher among males than females aged 11-20 years. We also characterised HBV and HDV strains circulating in the village. The principal HBV strains belonged to genotype HBV-E and subgenotype QS-A3. Complete genome analysis revealed for the first time the presence of the HBV-D genotype in Gabon, in the form of an HBV-D/E recombinant. Molecular analysis of HDV strains and their complete genomic characterisation revealed two distinct groups within the dominant HDV clade 8. Molecular analysis of HBV and HDV strains did not reveal vertical transmission within the families studied but rather horizontal, intrafamilial transmission among children aged 0-10 years. Our findings indicate that HBV is transmitted in early childhood by body fluids rather than by sexual contact. Health education adapted to the different age groups might therefore help to reduce HBV transmission. Young children should be vaccinated to control HBV infection in areas of extremely high prevalence.
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Affiliation(s)
- Sandrine François-Souquière
- Laboratoire de Virologie, Centre International de Recherches Médicales de Franceville, BP 769, Franceville, Gabon
| | - Maria Makuwa
- Laboratoire de Virologie, Centre International de Recherches Médicales de Franceville, BP 769, Franceville, Gabon
| | - Ulrich Bisvigou
- Laboratoire de Virologie, Centre International de Recherches Médicales de Franceville, BP 769, Franceville, Gabon
| | - Mirdad Kazanji
- Laboratoire de Virologie, Centre International de Recherches Médicales de Franceville, BP 769, Franceville, Gabon; Réseau International des Instituts Pasteur, Institut Pasteur de la Guyane, French Guiana, France.
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34
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Analysis of hepatitis B virus genotypes by restriction fragment length polymorphism. BIOMEDICA 2015; 36:79-88. [DOI: 10.7705/biomedica.v36i0.2976] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Indexed: 12/15/2022]
Abstract
<p><strong>Introducción.</strong> Se han descrito diez genotipos (A-J) del virus de la hepatitis B (HBV) que están distribuidos en todos los continentes. Una de las técnicas utilizadas para determinar el genotipo viral es el análisis del polimorfismo de longitud de los fragmentos de restricción, un método simple y económico, pero con algunas limitaciones.<br /><strong>Objetivo.</strong> El objetivo inicial del estudio fue identificar el genotipo del HBV mediante RFLP en muestras de suero obtenidas de pacientes y donantes de sangre. Sin embargo, por las discrepancias observadas en los patrones de RFLP fue necesario realizar análisis filogenéticos y un análisis in silico de secuencias del HBV.<br /><strong>Materiales y métodos.</strong> Se obtuvieron 56 muestras de suero. Tras la extracción de ADN, se amplificó un fragmento del ORF S del HBV mediante reacción en cadena de la polimerasa, cuyos productos se analizaron por RFLP con las enzimas <em>AlwI</em>, <em>BsrI</em>, <em>CfrI</em>, <em>HpaII</em> y <em>StyI</em>, y algunos se secuenciaron. Los patrones obtenidos se compararon con los reportados previamente. Se efectuó un análisis<em> in silico</em> de RFLP en consideración de las diferencias entre los patrones esperados y los observados.<br /><strong>Resultados.</strong> Se identificaron los genotipos A y F, subgenotipo F3, en las muestras. Este resultado coincide con lo descrito en estudios previos en los que se ha demostrado que el genotipo F, subgenotipo F3, es prevalente en la población de la región andina del país, en tanto que el genotipo A predomina en el occidente (departamento del Chocó). Con base en el análisis <em>in silico</em> de 229 secuencias virales obtenidas del GenBank y las 11 secuencias de este estudio, se caracterizó un nuevo patrón de RFLP específico para el genotipo F, subgenotipo F3, y se describieron algunas modificaciones en el patrón de RFLP del genotipo A, subgenotipo A1.<br /><strong>Conclusiones.</strong> Se caracterizó el patrón de genotipificación del genotipo F, subgenotipo F3, del HBV mediante RFLP, análisis in silico y secuenciación. Se requieren nuevos análisis in silico con un número mayor de secuencias para validar los patrones de RFLP de los genotipos y subgenotipos del VHB.</p>
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35
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Yacoubi L, Brichler S, Mansour W, Le Gal F, Hammami W, Sadraoui A, Ben Mami N, Msaddek A, Cheikh I, Triki H, Gordien E. Molecular epidemiology of hepatitis B and Delta virus strains that spread in the Mediterranean North East Coast of Tunisia. J Clin Virol 2015; 72:126-32. [PMID: 26513762 DOI: 10.1016/j.jcv.2015.10.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Revised: 09/28/2015] [Accepted: 10/04/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Tunisia is classified as an area of middle endemic for hepatitis B virus (HBV) infection, however little is known about hepatitis Delta virus (HDV) infection. OBJECTIVES This study aimed to address the prevalence of HDV infection, to identify possible risks factors, and to analyze the genetic diversity of HDV strains that are spreading in Tunisia. STUDY DESIGN A retrospective large-scale study including 1615 HBsAg positive patients, native of the North East coast of Tunisia, recruited from Gastroenterology departments, was conducted. Demographic, epidemiological, ethnical, clinical and biological data were recorded. HBV and HDV serological analyses and DNA and RNA viral load quantification were performed. Genotyping of HBV and HDV strains was performed using nucleotide sequencing followed by phylogenetic analyses. RESULTS The study population included 819 (50.7%) men and 796 (49.3%) women; aged 12-90 years (mean age 41±13 years). A very low prevalence of HDV infection, 2% was observed. No risk factor, except a history of hospitalization for surgery was found. All HDV strains belonged to genotype 1, with a wide distribution within the HDV-1 group. They all share the African amino acid marker, a serine at position 202 of the large Delta protein. HBV genotypes were distributed as follows: HBV/D1 (56.8%), HBV/D7 (40.9%), and HBV/A2 (2.3%). CONCLUSION Tunisia is a low endemic region for HDV infection, due to an efficient policy of HBV infection control. HDV-1 is the sole genotype found, with a high diversity within this group. Further studies are ongoing in order to better characterize and manage the HBV/HDV-infected patients according to the genetic variability of the viral strains.
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Affiliation(s)
- Lamia Yacoubi
- Laboratoire de Virologie Clinique, Institut Pasteur de Tunis, Tunisia; Carthage University, Tunis, Tunisia
| | - Ségolène Brichler
- Laboratoire de Bactériologie, Virologie, Hygiène, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, UFR Santé Médecine Biologie Humaine, Université Paris 13, Bobigny, France
| | - Wael Mansour
- Laboratoire de Bactériologie, Virologie, Hygiène, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, UFR Santé Médecine Biologie Humaine, Université Paris 13, Bobigny, France
| | - Frédéric Le Gal
- Laboratoire de Bactériologie, Virologie, Hygiène, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, UFR Santé Médecine Biologie Humaine, Université Paris 13, Bobigny, France
| | - Walid Hammami
- Laboratoire de Virologie Clinique, Institut Pasteur de Tunis, Tunisia
| | - Amel Sadraoui
- Laboratoire de Virologie Clinique, Institut Pasteur de Tunis, Tunisia
| | - Nabil Ben Mami
- Department of Gastroenterology B, La Rabta Hospital, Tunisia; Tunis El Manar University, Tunis, Tunisia
| | - Azouz Msaddek
- Department of Gastroenterology, Tahar Maamouri Hospital, Nabeul, Tunisia; Tunis El Manar University, Tunis, Tunisia
| | - Imed Cheikh
- Department of Gastroenterology, Habib Bougatfa Hospital, Bizerte, Tunisia; Tunis El Manar University, Tunis, Tunisia
| | - Henda Triki
- Laboratoire de Virologie Clinique, Institut Pasteur de Tunis, Tunisia; Tunis El Manar University, Tunis, Tunisia.
| | - Emmanuel Gordien
- Laboratoire de Bactériologie, Virologie, Hygiène, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, UFR Santé Médecine Biologie Humaine, Université Paris 13, Bobigny, France.
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Araujo NM. Hepatitis B virus intergenotypic recombinants worldwide: An overview. INFECTION GENETICS AND EVOLUTION 2015; 36:500-510. [PMID: 26299884 DOI: 10.1016/j.meegid.2015.08.024] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 08/11/2015] [Accepted: 08/19/2015] [Indexed: 02/07/2023]
Abstract
Novel variants generated by recombination events between different hepatitis B virus (HBV) genotypes have been increasingly documented worldwide, and the role of recombination in the evolutionary history of HBV is of significant research interest. In the present study, large-scale data retrieval and analysis on HBV intergenotypic recombinant genomes were performed. The geographical distribution of HBV recombinants as well as the molecular processes involved in recombination were examined. After review of published data, a total of 436 complete HBV sequences, previously identified as recombinants, were included in the recombination detection analysis. About 60% of HBV recombinants were B/C (n=179) and C/D (n=83) hybrids. A/B/C, A/C, A/C/G, A/D, A/E, A/G, B/C/U (U=unknown genotype), C/F, C/G, C/J, D/E, D/F, and F/G hybrids were additionally identified. HBV intergenotypic sequences were reported in almost all geographical regions with similar circulation patterns as their original genotypes, indicating the potential for spreading in a wide range of human populations and developing their own epidemiology. Recombination breakpoints were non-randomly distributed in the genome, and specific favored sites detected, such as within nt 1700-2000 and 2100-2300 regions, which displayed a statistically significant difference in comparison with the remaining genome. Elucidation of the effects of recombination events on the evolutionary history of HBV is critical to understand current and future evolution trends.
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Affiliation(s)
- Natalia M Araujo
- Laboratório de Virologia Molecular, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, 21040-360 Rio de Janeiro, RJ, Brazil.
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El Hadad S, Alakilli S, Rabah S, Sabir J. Identification of Novel D11 Hepatitis B Surface Antigen Subgenotype in Jeddah, Kingdom of Saudi Arabia. BIOTECHNOLOGY(FAISALABAD) 2015; 14:119-128. [DOI: 10.3923/biotech.2015.119.128] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Epidemiology of HBV subgenotypes D. Clin Res Hepatol Gastroenterol 2015; 39:28-37. [PMID: 25037178 DOI: 10.1016/j.clinre.2014.06.005] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2013] [Revised: 04/09/2014] [Accepted: 06/02/2014] [Indexed: 02/04/2023]
Abstract
The natural history of hepatitis B virus infection is not uniform and affected from several factors including, HBV genotype. Genotype D is a widely distributed genotype. Among genotype D, several subgenotypes differentiate epidemiologically and probably clinically. D1 is predominant in Middle East and North Africa, and characterized by early HBeAg seroconversion and low viral load. D2 is seen in Albania, Turkey, Brazil, western India, Lebanon, and Serbia. D3 was reported from Serbia, western India, and Indonesia. It is a predominant subgenotype in injection drug use-related acute HBV infections in Europe and Canada. D4 is relatively rare and reported from Haiti, Russia and Baltic region, Brazil, Kenya, Morocco and Rwanda. Subgenotype D5 seems to be common in Eastern India. D6 has been reported as a rare subgenotype from Indonesia, Kenya, Russia and Baltic region. D7 is the main genotype in Morocco and Tunisia. D8 and D9 are recently described subgenotypes and reported from Niger and India, respectively. Subgenotypes of genotype D may have clinical and/or viral differences. More subgenotype studies are required to conclude on subgenotype and its clinical/viral characteristics.
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Tran H, Yu ML, Dai CY, Lin IL, Yeh ML, Chuang WL, Abe K. Novel quasi-subgenotype D2 of hepatitis B virus identified in Taiwanese aborigines. Virus Genes 2014; 49:30-37. [PMID: 24792512 DOI: 10.1007/s11262-014-1072-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Accepted: 04/08/2014] [Indexed: 01/05/2023]
Abstract
The hepatitis B virus (HBV) genomes in Taiwanese aborigines, whose ancestors have lived in Taiwan for over 10,000 years, have not been characterized. In order to characterize of HBV in this special population, serum samples were obtained from serologically HBsAg-positive 27 Taiwanese aborigines. The pre-S1/S2 region and the full-length 3.2 kb of the HBV genome were amplified by PCR. Obtained amplicons were sequenced and confirmed the HBV genotypes by phylogenetic analysis. By phylogenetic analysis of the sequence of pre-S1/pre-S2 region, HBV/B2 (21/27: 78 %) was the most prevalent followed by genotype D (6/27: 22 %). Two strains of HBV/B2, each having 3,215 bp genomes, had recombination with genotype C in the pre-C/C gene which is characteristic of subgenotype B2 circulating in Southeast Asia. Interestingly, six strains of genotype D formed a distinct cluster between subgenotypes D1 and D2 suggesting a novel group of HBV. A similar finding could also be confirmed based on the entire 3,182 bp genome from four strains of HBV/D. This new cluster was supported by a branch with 99 % bootstrap value and 3.4-5.8 % nucleotide divergence over the entire genome from other known subgenotypes D1 to D9. Four strains of the new D subgenotype showed serotype ayw2, but had unique amino acid sequences consisting of N115 in the preS/S gene; P41 in the X gene; S239, K/E295, V567, and P708 in the P gene, respectively. From the above results, we provisionally proposed to designate it as novel quasi-subgenotype D2 identified in Taiwanese aborigines.
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Affiliation(s)
- Huy Tran
- Division of Gastroenterology, Internal Medicine Department, University of Iowa Hospitals and Clinics, Iowa, IA, USA
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Gallego F, Pisano MB, Torres C, Caeiro L, Martínez Wassaf M, Balangero M, Campos R, Ré V. Molecular epidemiology of hepatitis B virus in Córdoba, Argentina. J Clin Virol 2014; 61:204-10. [PMID: 25066884 DOI: 10.1016/j.jcv.2014.06.030] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 06/09/2014] [Accepted: 06/26/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND The analysis of the genomes of hepatitis B virus (HBV) identifies phylogenetic variants called genotypes, which may lead to distinct biological and clinical behaviors. OBJECTIVES The aim of this study was to describe the current molecular epidemiology and genetic diversity of HBV in Córdoba, Argentina. STUDY DESIGN A total of 52 HBV samples, 40 from HBV mono-infected and 12 from human immunodeficiency virus (HIV)-HBV co-infected patients, were sequenced in the S gene and in the basal core promoter-precore (BCP-pC) region. RESULTS Presence of subgenotypes F1b (35%) and F4 (17.5%), subgenotype A2 (37.5%), C (5.0%) (subgenotype could not be defined) and D (5.0%) (subgenotype D2, and the other could not be defined) were observed among mono-infected patients. The co-infected individuals displayed a different genotype distribution: sub-genotype A2 was the most common (75.0%), followed by subgenotype F1b (25.0%). CONCLUSIONS These results showed two epidemiologic scenarios: the mono-infected population may represent the ethnic composition of the current human population of Córdoba, where the Amerindian (genotype F) and European origins (subgenotype A2) account for the 90% of the samples; for the co-infected patients, the high prevalence of subgenotype A2 resemble previous analyses from Buenos Aires. In addition, mutations in hepatitis B surface antigen (HBsAg), polymerase and BCP-pC regions were identified, mainly in chronic or co-infected patients.
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Affiliation(s)
- Fernando Gallego
- Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016 Córdoba, Argentina.
| | - María Belén Pisano
- Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016 Córdoba, Argentina.
| | - Carolina Torres
- Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 4° piso, C1113AAD Ciudad Autónoma de Buenos Aires, Argentina.
| | - Luciana Caeiro
- Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016 Córdoba, Argentina.
| | - Maribel Martínez Wassaf
- Laboratorio de Análisis Clínicos Especializados-LACE, Vélez Sársfield 528, CP 5000 Córdoba, Argentina.
| | - Marcos Balangero
- Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016 Córdoba, Argentina.
| | - Rodolfo Campos
- Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 4° piso, C1113AAD Ciudad Autónoma de Buenos Aires, Argentina.
| | - Viviana Ré
- Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Enfermera Gordillo Gómez s/n, Ciudad Universitaria, CP 5016 Córdoba, Argentina.
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Zehender G, Ebranati E, Gabanelli E, Sorrentino C, Lo Presti A, Tanzi E, Ciccozzi M, Galli M. Enigmatic origin of hepatitis B virus: An ancient travelling companion or a recent encounter? World J Gastroenterol 2014; 20:7622-7634. [PMID: 24976700 PMCID: PMC4069291 DOI: 10.3748/wjg.v20.i24.7622] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 01/08/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) is the leading cause of liver disease and infects an estimated 240 million people worldwide. It is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral replication. The ten genotypes (A-J) that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic distribution. Genotypes A and D are ubiquitous and the most prevalent genotypes in Europe (mainly represented by subgenotypes D1-3 and A2); genotypes B and C are restricted to eastern Asia and Oceania; genotype E to central and western Africa; and genotypes H and F (classified into 4 subgenotypes) to Latin America and Alaska. This review summarises the data obtained by studying the global phylodynamics and phylogeography of HBV genotypes, particularly those concerning the origin and dispersion histories of genotypes A, D, E and F and their subgenotypes. The lack of any consensus concerning the HBV substitution rate and the conflicting data obtained using different calibration approaches make the time of origin and divergence of the various genotypes and subgenotypes largely uncertain. It is hypothesised that HBV evolutionary rates are time dependent, and that the changes depend on the main transmission routes of the genotypes and the dynamics of the infected populations.
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Bonvicino CR, Moreira MA, Soares MA. Hepatitis B virus lineages in mammalian hosts: Potential for bidirectional cross-species transmission. World J Gastroenterol 2014; 20:7665-7674. [PMID: 24976704 PMCID: PMC4069295 DOI: 10.3748/wjg.v20.i24.7665] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 12/30/2013] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
The hepatitis B virus (HBV) is a cosmopolitan infectious agent currently affecting over 350 million people worldwide, presently accounting for more than two billion infections. In addition to man, other hepatitis virus strains infect species of several mammalian families of the Primates, Rodentia and Chiroptera orders, in addition to birds. The mounting evidence of HBV infection in African, Asian and neotropical primates draws attention to the potential cross-species, zoonotic transmission of these viruses to man. Moreover, recent evidence also suggests the humans may also function as a source of viral infection to other mammals, particularly to domestic animals like poultry and swine. In this review, we list all evidence of HBV and HBV-like infection of nonhuman mammals and discuss their potential roles as donors or recipients of these viruses to humans and to other closely-related species.
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Pourkarim MR, Amini-Bavil-Olyaee S, Kurbanov F, Van Ranst M, Tacke F. Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions. World J Gastroenterol 2014; 20:7152-68. [PMID: 24966586 PMCID: PMC4064061 DOI: 10.3748/wjg.v20.i23.7152] [Citation(s) in RCA: 146] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Revised: 11/28/2013] [Accepted: 01/02/2014] [Indexed: 02/06/2023] Open
Abstract
The clinical course of infections with the hepatitis B virus (HBV) substantially varies between individuals, as a consequence of a complex interplay between viral, host, environmental and other factors. Due to the high genetic variability of HBV, the virus can be categorized into different HBV genotypes and subgenotypes, which considerably differ with respect to geographical distribution, transmission routes, disease progression, responses to antiviral therapy or vaccination, and clinical outcome measures such as cirrhosis or hepatocellular carcinoma. However, HBV (sub)genotyping has caused some controversies in the past due to misclassifications and incorrect interpretations of different genotyping methods. Thus, an accurate, holistic and dynamic classification system is essential. In this review article, we aimed at highlighting potential pitfalls in genetic and phylogenetic analyses of HBV and suggest novel terms for HBV classification. Analyzing full-length genome sequences when classifying genotypes and subgenotypes is the foremost prerequisite of this classification system. Careful attention must be paid to all aspects of phylogenetic analysis, such as bootstrapping values and meeting the necessary thresholds for (sub)genotyping. Quasi-subgenotype refers to subgenotypes that were incorrectly suggested to be novel. As many of these strains were misclassified due to genetic differences resulting from recombination, we propose the term "recombino-subgenotype". Moreover, immigration is an important confounding facet of global HBV distribution and substantially changes the geographic pattern of HBV (sub)genotypes. We therefore suggest the term "immigro-subgenotype" to distinguish exotic (sub)genotypes from native ones. We are strongly convinced that applying these two proposed terms in HBV classification will help harmonize this rapidly progressing field and allow for improved prophylaxis, diagnosis and treatment.
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Ducancelle A, Abgueguen P, Birguel J, Mansour W, Pivert A, Le Guillou-Guillemette H, Sobnangou JJ, Rameau A, Huraux JM, Lunel-Fabiani F. High endemicity and low molecular diversity of hepatitis B virus infections in pregnant women in a rural district of North Cameroon. PLoS One 2013; 8:e80346. [PMID: 24265811 PMCID: PMC3827216 DOI: 10.1371/journal.pone.0080346] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2013] [Accepted: 10/01/2013] [Indexed: 02/07/2023] Open
Abstract
Background A program, supported by the GEMHEP (Groupe d'étude Moléculaire des Hépatites), was established in 2007 in the sanitary district of Tokombéré, to prevent perinatal transmission of hepatitis B virus (HBV). It comprises screening for HBV surface antigen (HBsAg) in all pregnant women and vaccinating the newborn if tests are positive. Methods/Principal Findings 1276 women were enrolled in the study after providing informed consent. Demographic data and blood samples were available for 1267 of the enrolled patients. HBsAg was determined locally using a rapid test (Vikia HBsAg, Biomerieux). Tests for HBV and HDV virological markers (HBeAg, anti-HDV antibodies (Ab), HBV-DNA, HDV-RNA, HBV and HDV genotypes) were performed on the confirmed HBsAg-positive samples in the virology unit of the Angers University Hospital (France). HBsAg was found in 259 of the 1267 pregnant women (20.4%) between January 2009 and April 2010, of whom 59 were HBeAg-positive (22.7%) with high levels of HBV-DNA. Anti-HDV Ab were found in 19 (7.3%) of the HBsAg-positive women. The prevalence rates of HBsAg and HDV were not age-dependent whereas HBeAg carriers were statistically younger than non carriers. Basal core promoter (BCP) and precore (PC) mutations and genotypes were determined by sequencing. Of 120 amplified sequences, 119 belonged to HBV genotype E (HBV/E) and the 9 HDV strains belonged to HDV clade 1. In the PC region, 83/228 patients (36.4%) harbored a G1896A mutant or mixed phenotype virus. In the BCP region, the double mutation A1762T/G1764A and the G1757A substitution were detected respectively in 26/228 patients (11.4%) and 189/228 patients (82.8%). Conclusions Our results confirm the high prevalence and low molecular diversity of HBV in Far Northern Cameroon; more than 20% of the infected women were highly viremic, suggesting a high rate of HBV perinatal transmission and supporting the WHO recommendation to vaccinate at birth against hepatitis B.
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Affiliation(s)
- Alexandra Ducancelle
- Department of Bacteriology and Virology, Angers University Hospital, and HIFIH Laboratory, UPRES 3859, SFR 4208, Angers Cedex 9, France
- * E-mail:
| | - Pierre Abgueguen
- Department of Infectious Diseases and Internal Medicine, Angers University Hospital, Angers Cedex 9, France
| | | | - Wael Mansour
- Department of Bacteriology and Virology, Angers University Hospital, and HIFIH Laboratory, UPRES 3859, SFR 4208, Angers Cedex 9, France
| | - Adeline Pivert
- Department of Bacteriology and Virology, Angers University Hospital, and HIFIH Laboratory, UPRES 3859, SFR 4208, Angers Cedex 9, France
| | - Hélène Le Guillou-Guillemette
- Department of Bacteriology and Virology, Angers University Hospital, and HIFIH Laboratory, UPRES 3859, SFR 4208, Angers Cedex 9, France
| | | | - Amélie Rameau
- Department of Bacteriology and Virology, Angers University Hospital, and HIFIH Laboratory, UPRES 3859, SFR 4208, Angers Cedex 9, France
| | - Jean-Marie Huraux
- Virology Laboratory, Hospital AP-HP Pitié-Salpêtrière, ER1 DETIV, University Paris VI Pierre et Marie Curie, France
| | - Françoise Lunel-Fabiani
- Department of Bacteriology and Virology, Angers University Hospital, and HIFIH Laboratory, UPRES 3859, SFR 4208, Angers Cedex 9, France
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Brichler S, Lagathu G, Chekaraou MA, Le Gal F, Edouard A, Dény P, Césaire R, Gordien E. African, Amerindian and European hepatitis B virus strains circulate on the Caribbean Island of Martinique. J Gen Virol 2013; 94:2318-2329. [PMID: 23884366 DOI: 10.1099/vir.0.055459-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Ten Hepatitis B virus (HBV) genotypes, as well as numerous subgenotypes, have been described in well-characterized ethnogeographical populations. Martinique has been at a crossroads between Africa, Europe, India and the Americas because of the slave trade (17th-19th centuries), followed by an important immigration of Indian and West African workers. In this work, we aimed to study the molecular epidemiology of HBV infection in Martinique according to this unique settlement pattern. To that end, blood samples from 86 consecutive HBV-infected patients from the main hospitals of the island, were retrospectively analysed. Direct sequencing of the pre-S1 or pre-C-C region or complete genome sequencing, followed by phylogenetic analyses were performed. HBV genotypes were: HBV/A1 (68.6 %), HBV/A2 (10.5 %), HBV/D, mainly HBV/D3 and HBV/D4 (8.1 %), HBV/F (3.5 %), and also HBV/E (2.3 %), two strains isolated from two West-African patients. Moreover, 74 % of the HBeAg-negative strains harboured classical pre-C-C mutations, and most HBV/A1 strains also containing specific mutations. Finally, various patterns of deletion mutants in pre-S and pre-C-C regions were found. In conclusion, our findings point to historical and migration-related issues in HBV-genotype distribution suggesting that HBV/A1, but not HBV/E, was imported from Africa during the slave trade, and further supporting the hypothesis that HBV/E has emerged recently in West Africa (<150 years). Potential origins of 'European' HBV/A2 and HBV/D3, 'Amerindian' HBV/F, and HBV/D4 strains are also discussed. Such HBV genetic diversity, beyond its epidemiological interest, may have a clinical impact on the natural history of HBV infection in Martinique.
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Affiliation(s)
- Ségolène Brichler
- Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
| | - Gisèle Lagathu
- Service de Bactériologie, Virologie du Centre Hospitalier Régional et Universitaire de Rennes, Pontchaillou, France
| | - Mariama Abdou Chekaraou
- Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
| | - Frédéric Le Gal
- Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
| | - André Edouard
- Service d'Hépato-Gastro-Entérologie, Centre Hospitalier Universitaire de Fort-de-France, Martinique, France
| | - Paul Dény
- Centre de Recherche sur le Cancer, Équipe 16, INSERM U1052, CNRS UMR 5286, Lyon, France.,Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
| | - Raymond Césaire
- Laboratoire de Virologie, Centre Hospitalier Universitaire de Fort-de-France, Martinique; EA 4537, Université Antilles-Guyane, France
| | - Emmanuel Gordien
- Service de Bactériologie, Virologie-Hygiène, Assistance Publique-Hôpitaux de Paris; Hôpitaux Universitaires de Paris Seine Saint-Denis, Site Avicenne, Bobigny; Laboratoire Associé au Centre National de Référence des Hépatites B, C et Delta, Université Paris Nord, Sorbonne Paris Cité, France
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Molecular characterization of hepatitis B virus in liver disease patients and asymptomatic carriers of the virus in Sudan. BMC Infect Dis 2013; 13:328. [PMID: 23865777 PMCID: PMC3722059 DOI: 10.1186/1471-2334-13-328] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2013] [Accepted: 07/16/2013] [Indexed: 12/12/2022] Open
Abstract
Background Hepatitis B virus is hyperendemic in Sudan. Our aim was to molecularly characterize hepatitis B virus from Sudanese individuals, with and without liver disease, because genotypes play an important role in clinical manifestation and treatment management. Methods Ninety-nine patients - 30 asymptomatic, 42 cirrhotic, 15 with hepatocellular carcinoma, 7 with acute hepatitis and 5 with chronic hepatitis- were enrolled. Sequencing of surface and basic core promoter/precore regions and complete genome were performed. Results The mean ± standard deviation, age was 45.7±14.8 years and the male to female ratio 77:22. The median (interquartile range) of hepatitis B virus DNA and alanine aminotransferase levels were 2.8 (2.2-4.2) log IU/ml and 30 (19–49) IU/L, respectively. Using three genotyping methods, 81/99 (82%) could be genotyped. Forty eight percent of the 99 patients were infected with genotype D and 24% with genotype E, 2% with putative D/E recombinants and 7% with genotype A. Patients infected with genotype E had higher frequency of hepatitis B e antigen-positivity and higher viral loads compared to patients infected with genotype D. Basic core promoter/precore region mutations, including the G1896A in 37% of HBeAg-negative individuals, could account for hepatitis B e antigen-negativity. Pre-S deletion mutants were found in genotypes D and E. Three isolates had the vaccine escape mutant sM133T. Conclusion Sudanese hepatitis B virus carriers were mainly infected with genotypes D or E, with patients infected with genotype E having higher HBeAg-positivity and higher viral loads. This is the first study to molecularly characterize hepatitis B virus from liver disease patients in Sudan.
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Impact of hepatitis B and delta virus co-infection on liver disease in Mauritania: a cross sectional study. J Infect 2013; 67:448-57. [PMID: 23796871 DOI: 10.1016/j.jinf.2013.06.008] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Revised: 05/22/2013] [Accepted: 06/05/2013] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Mauritania is a highly endemic region for hepatitis B (HBV) and delta (HDV) viruses. No data are available on HDV's impact on the severity of liver disease in consecutive HBV-infected patients in Africa. This study evaluated the degree of liver fibrosis in a cohort of chronic HBV carriers. METHODS Three-hundred consecutive HBV-infected Mauritanian patients were checked for HDV infection via the detection of anti-HDV antibodies (Ab) and viral RNA. HBV- vs. HBV/HDV-infected patients were compared by physical examination, biological analyses, and the APRI (aspartate aminotransferase to platelet ratio index) and FibroMeter tests for determination of liver fibrosis. RESULTS More than 30% of the patients had anti-HDVAb. Among these, 62.2% were HDV-RNA positive. Co-infected patients were older (>8-years) than HBV-mono-infected patients. They had more liver tests abnormalities and clinical or ultrasound signs of liver fibrosis. APRI and FibroMeter scores were also significantly increased in these patients. In multivariate analysis, beyond HDVAb, male gender and HBV-VL >3.7 log IU/mL were the only markers linked to significant liver fibrosis. CONCLUSIONS In Mauritania, HDV co-infection worsens liver disease, both clinically and biologically, as confirmed by the APRI and FibroMeter tests. These tests may be useful for the management of delta hepatitis, which is a major health problem in Mauritania.
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Yousif M, Kramvis A. Genotype D of hepatitis B virus and its subgenotypes: An update. Hepatol Res 2013; 43:355-64. [PMID: 22978460 DOI: 10.1111/j.1872-034x.2012.01090.x] [Citation(s) in RCA: 62] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2012] [Revised: 08/16/2012] [Accepted: 08/19/2012] [Indexed: 12/17/2022]
Abstract
AIM The aim of the present study was to systematically and comparatively analyze the subgenotypes of genotype D of hepatitis B virus. METHODS In total, 304 complete genomes of all genotype D subgenotypes were downloaded from the public databases. The sequences were analyzed using nucleotide divergence calculations, phylogenetic analysis and bioinformatics to detect amino acids signature motifs for each subgenotype and to define their geographical distribution. RESULTS Intragroup divergence ranged from 0.8 ± 0.5 (% standard deviation) for subgenotype D6 to 3.0 ± 0.3 for D8. Inter-subgenotype divergence mostly ranged 4-7.5%. Phylogenetic analysis of genotype D showed separation into six distinct clusters (subgenotypes D1, D2, D3/D6, D4, D5 and D7/D8) with good bootstrap support. The mean intergroup divergence between D3 and D6 was the lowest and fell below the threshold of 4%, which is required to define a subgenotype, suggesting that subgenotypes D3 and D6 belong to one subgenotype. "D8" is a genotype D/E recombinant, which clusters with D7. A number of signature amino acids were found in all four open reading frames that could differentiate the subgenotypes, which also showed distinct geographical distribution. CONCLUSION There are six and not eight subgenotypes of D, D1-D6, which can be differentiated by distinct clustering with high bootstrap support and signature amino acids. Subgenotypes D3 and "D6" should be reclassified as a single subgenotype D3 and it would be more correct to classify "D8" as a genotype D/E recombinant rather than a subgenotype.
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Affiliation(s)
- Mukhlid Yousif
- Hepatitis Virus Diversity Research Programme, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Hepatitis B virus subgenotyping: history, effects of recombination, misclassifications, and corrections. INFECTION GENETICS AND EVOLUTION 2013; 16:355-61. [PMID: 23538336 DOI: 10.1016/j.meegid.2013.03.021] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/06/2012] [Revised: 03/15/2013] [Accepted: 03/16/2013] [Indexed: 12/23/2022]
Abstract
Hepatitis B virus (HBV) has evolved into phylogenetically separable genotypes and subgenotypes. Accurately assigning the subgenotype for an HBV strain is of clinical and epidemiological significance. In this paper, we review the recommendations currently employed for HBV subgenotyping, the history of HBV subgenotyping, the effects of recombination on HBV subgenotyping, misclassifications in HBV subgenotyping, and suggestions are made to correct the misclassifications. Finally, proposals are made to guide future HBV subgenotyping.
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Ghosh S, Banerjee P, Deny P, Mondal RK, Nandi M, Roychoudhury A, Das K, Banerjee S, Santra A, Zoulim F, Chowdhury A, Datta S. New HBV subgenotype D9, a novel D/C recombinant, identified in patients with chronic HBeAg-negative infection in Eastern India. J Viral Hepat 2013; 20:209-18. [PMID: 23383660 DOI: 10.1111/j.1365-2893.2012.01655.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2012] [Accepted: 07/02/2012] [Indexed: 02/06/2023]
Abstract
Genome diversity is a hallmark of hepatitis B virus (HBV), which allowed its classification into 10 genotypes (A-J) and numerous subgenotypes. Among them, Genotype D is currently segregated into eight subgenotypes (D1-D8). Here, we report the identification and characterization of a novel subgenotype within genotype D of HBV from chronic hepatitis B e antigen (HBeAg)-negative patients of Eastern India. Phylogenetic tree analysis based on complete genome sequences revealed that six of 39 HBV/D isolates formed a distinct cluster supported by high bootstrap value and had nucleotide divergence >4% relative to the known D subgenotypes (D1-D8), justifying their assignment into a new subgenotype (D9). By comparing the amino acid sequences of the four ORFs of HBV/D9 with D1-D8, 36 specific residues, including a unique one (E(112) in the core region), were identified that could be considered as a signature of D9. Further analysis by Simplot, BootScan and jpHMM demonstrated that D9 resulted from a discrete recombination with genotype C over the precore-core region. This type of recombination has not been described previously as all C/D recombinants reported so far possessed genotype C backbones with mosaic fragments derived from HBV/D. Interestingly, compared to other subgenotypes of HBV/D, D9 isolates had a higher frequency of mutations (A1762T and G1764A) in the basal core promoter region that had been implicated in the development of hepatocellular carcinoma. Further investigations are needed to determine the overall prevalence and clinical significance of these newly characterized D9 strains and to assess the impact of inter-genotypic recombination on viral properties.
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Affiliation(s)
- S Ghosh
- Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education and Research, Kolkata, India
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