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Investigation of Torque Teno Virus (TTV) DNA as an immunological and virological marker in pediatric hematopoietic stem cell transplantation (HSCT) patients. Microb Pathog 2020; 149:104397. [DOI: 10.1016/j.micpath.2020.104397] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 07/05/2020] [Accepted: 07/13/2020] [Indexed: 12/12/2022]
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2
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Bouquet J, Li T, Gardy JL, Kang X, Stevens S, Stevens J, VanNess M, Snell C, Potts J, Miller RR, Morshed M, McCabe M, Parker S, Uyaguari M, Tang P, Steiner T, Chan WS, De Souza AM, Mattman A, Patrick DM, Chiu CY. Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing. PLoS One 2019; 14:e0212193. [PMID: 30897114 PMCID: PMC6428308 DOI: 10.1371/journal.pone.0212193] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 01/24/2019] [Indexed: 11/19/2022] Open
Abstract
Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n = 14) and matched sedentary controls (n = 11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing reduced oxygen consumption ([Formula: see text]) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P = 0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.
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Affiliation(s)
- Jerome Bouquet
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America
| | - Tony Li
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America
| | - Jennifer L. Gardy
- Communicable Disease Prevention and Control Services, Vancouver, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, Canada
| | - Xiaoying Kang
- School of Population and Public Health, University of British Columbia, Vancouver, Canada
| | - Staci Stevens
- Workwell Foundation, Ripon, California, United States of America
| | - Jared Stevens
- Workwell Foundation, Ripon, California, United States of America
| | - Mark VanNess
- Workwell Foundation, Ripon, California, United States of America
| | | | - James Potts
- Department of Pediatrics, Division of Cardiology, University of British Columbia, Vancouver, Canada
| | - Ruth R. Miller
- School of Population and Public Health, University of British Columbia, Vancouver, Canada
| | - Muhammad Morshed
- British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, Canada
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
| | - Mark McCabe
- Communicable Disease Prevention and Control Services, Vancouver, Canada
| | - Shoshana Parker
- Centre for Health Evaluation Outcome Sciences, Vancouver, Canada
| | - Miguel Uyaguari
- British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, Canada
| | - Patrick Tang
- Department of Pathology, Sidra Medical and Research Center, Doha, Qatar
| | - Theodore Steiner
- Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada
| | - Wee-Shian Chan
- Department of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, Canada
| | | | - Andre Mattman
- Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
- Adult Metabolic Disease Clinic, Vancouver General Hospital, Vancouver, Canada
| | - David M. Patrick
- Communicable Disease Prevention and Control Services, Vancouver, Canada
- School of Population and Public Health, University of British Columbia, Vancouver, Canada
| | - Charles Y. Chiu
- Department of Laboratory Medicine, University of California San Francisco, San Francisco, California, United States of America
- Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, California, United States of America
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Xu L, Zhu Y, Ren L, Xu B, Liu C, Xie Z, Shen K. Characterization of the nasopharyngeal viral microbiome from children with community-acquired pneumonia but negative for Luminex xTAG respiratory viral panel assay detection. J Med Virol 2017; 89:2098-2107. [PMID: 28671295 PMCID: PMC7166964 DOI: 10.1002/jmv.24895] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 05/17/2017] [Indexed: 12/24/2022]
Abstract
In the present study, 50 nasopharyngeal swabs from children with community‐acquired pneumonia (CAP) but negative for 18 common respiratory viruses, as measured by the Luminex xTAG Respiratory Viral Panel Assay, were subjected to multiplex metagenomic analyses using a next‐generation sequencing platform. Taxonomic analysis showed that all sequence reads could be assigned to a specific species. An average of 95.13% were assigned to the Bacteria kingdom, whereas, only 0.72% were potentially virus derived. This snapshot of the respiratory tract virome revealed most viral reads to be respiratory tract related, classified into four known virus families: Paramyxoviridae, Herpesviridae, Anelloviridae, and Polyomaviridae. Importantly, we detected a novel human parainfluenza virus 3 (HPIV 3) strain with a 32‐bp insertion in the haemagglutinin‐neuraminidase (HN) gene that produced a negative result in the Luminex assay, highlighting the strength of virome metagenomic analysis to identify not only novel viruses but also viruses likely to be missed by ordinary clinical tests. Thus, virome metagenomic analysis could become a viable clinical diagnostic method.
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Affiliation(s)
- Lili Xu
- MOE Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics, National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Yun Zhu
- MOE Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics, National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Lili Ren
- Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS), Beijing, China
| | - Baoping Xu
- MOE Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics, National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Chunyan Liu
- MOE Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics, National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Zhengde Xie
- MOE Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics, National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Kunling Shen
- MOE Key Laboratory of Major Diseases in Children, National Key Discipline of Pediatrics, National Clinical Research Center for Respiratory Diseases, Beijing Key Laboratory of Pediatric Respiratory Infection diseases, Beijing Children's Hospital, Capital Medical University, Beijing, China
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Waterborne Viruses and F-Specific Coliphages in Mixed-Use Watersheds: Microbial Associations, Host Specificities, and Affinities with Environmental/Land Use Factors. Appl Environ Microbiol 2017; 83:AEM.02763-16. [PMID: 27836843 DOI: 10.1128/aem.02763-16] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 11/08/2016] [Indexed: 02/06/2023] Open
Abstract
From the years 2008 to 2014, a total of 1,155 water samples were collected (spring to fall) from 24 surface water sampling sites located in a mixed-used but predominantly agricultural (i.e., dairy livestock production) river basin in eastern Ontario, Canada. Water was analyzed for viable F-specific DNA (F-DNA) and F-specific RNA (F-RNA) (genogroup I [GI] to GIV) coliphage and a suite of molecularly detected viruses (norovirus [GI to GIV], torque teno virus [TTV], rotavirus, kobuvirus, adenovirus, astrovirus, hepatitis A, and hepatitis E). F-DNA and F-RNA coliphage were detected in 33 and 28% of the samples at maximum concentrations of 2,000 and 16,300 PFU · 100 ml-1, respectively. Animal TTV, human TTV, kobuvirus, astrovirus, and norovirus GIII were the most prevalent viruses, found in 23, 20, 13, 12, and 11% of samples, respectively. Viable F-DNA coliphage was found to be a modest positive indicator of molecularly detected TTV. F-RNA coliphage, unlike F-DNA coliphage, was a modest positive predictor of norovirus and rotavirus. There were, however, a number of significant negative associations among F-specific coliphage and viruses. F-DNA coliphage densities of >142 PFU · 100 ml-1 delineated conditions when ∼95% of water samples contained some type of virus. Kobuvirus was the virus most strongly related to detection of any other virus. Land use had some associations with virus/F-specific coliphage detection, but season and surface water flow were the variables that were most important for broadly delineating detection. Higher relative levels of detection of human viruses and human F-RNA coliphage were associated with higher relative degrees of upstream human land development in a catchment. IMPORTANCE This study is one of the first, to our knowledge, to evaluate relationships among F-specific coliphages and a large suite of enteric viruses in mixed-use but agriculturally dominated surface waters in Canada. This study suggested that relationships between viable F-specific coliphages and molecularly detected viruses do exist, but they are not always positive. Caution should be employed if viable F-specific coliphages are to be used as indicators of virus presence in surface waters. This study elucidates relative effects of agriculture, wildlife, and human activity on virus and F-specific coliphage detection. Seasonal and meteorological attributes play a strong role in the detection of most virus and F-specific coliphage targets.
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Hettmann A, Demcsák A, Bach Á, Decsi G, Dencs Á, Pálinkó D, Rovó L, Nagy K, Minarovits J, Takács M. Detection and Phylogenetic Analysis of Torque Teno Virus in Salivary and Tumor Biopsy Samples from Head and Neck Carcinoma Patients. Intervirology 2016; 59:123-129. [DOI: 10.1159/000452974] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Accepted: 10/31/2016] [Indexed: 11/19/2022] Open
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Abbasi S, Makvandi M, Karimi G, Neisi N. The Prevalence of SEN Virus and Occult Hepatitis B (OBI) Virus Infection Among Blood Donors in Ahvaz City. Jundishapur J Microbiol 2016; 9:e37329. [PMID: 27679708 PMCID: PMC5035438 DOI: 10.5812/jjm.37329] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Revised: 05/31/2016] [Accepted: 06/21/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The SEN virus (SENV) is a prevalent blood borne pathogen that has a worldwide incidence. SENV is comprised of eight genotypes; genotypes H and D are frequently associated with the pathogenesis of non-A - E hepatitis and post-transfusion hepatitis in blood donors and hepatitis patients. So far, no SENV pathogenesis has been reported in the liver biopsies of SENV carriers, but the frequency of SENV and its related genotypes requires further molecular epidemiology studies in different regions of the world. Occult hepatitis B infection (OBI) is another global public health problem that is primarily transmitted via blood transfusions. Therefore, the identification of OBI among blood donors is key to preventing the spread of this disease. The relationship between SENV and OBI requires further evaluation. OBJECTIVES The aim of this study was to determine the prevalence of SENV-D and SENV-H in blood donors in Ahvaz city with a particular focus on co-infection with OBI. PATIENTS AND METHODS This study had a cross-sectional design and included 184 healthy consecutive blood donors who visited a blood transfusion center in Ahvaz city from October-November 2013. The sera of all blood donors negative for HBsAg, anti-HCV antibody, and anti-HIV antibody were tested for SENV-D and SENV-H using nested polymerase chain reaction (PCR). In addition, tests for HBV DNA (PCR), HBcIgG (ELISA), liver function (aspartate transaminase and alanine transaminase), and alkaline phosphatase were carried out. RESULTS Liver function tests in the healthy blood donors were within the normal range. The incidence rates of SENV-D and SENV-H in the 184 total blood donors were 10 (5.4%) (95% confidence interval (CI): 2.1% - 9.0%) and 32 (17.4%) cases (95% CI: 12.0% - 23.0%), respectively. SENV-H/D co-infection occurred in 2 (1.1%) patients. The sera of 8/184 (4.3%) were positive for anti-HBc antibody but negative for HBV DNA. CONCLUSIONS Regardless of the presence of nonpathogenic SENV, 44/184 (24%) blood donors tested positive for both SENV-D and SENV-H. Although 4.3% of blood donors were positive for HBcIgG but negative for HBV DNA, the presence of OBI cannot be ruled out unless their liver biopsies show negative for HBV DNA.
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Affiliation(s)
- Samaneh Abbasi
- Health Research Institute, Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
- Department of Virology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Manoochehr Makvandi
- Health Research Institute, Infectious and Tropical Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
- Department of Virology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Gharib Karimi
- Iranian Blood Transfusion Organization (IBTO), Tehran, IR Iran
| | - Niloofar Neisi
- Department of Virology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
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Lee Y, Lin CM, Jeng CR, Chang HW, Chang CC, Pang VF. The pathogenic role of torque teno sus virus 1 and 2 and their correlations with various viral pathogens and host immunocytes in wasting pigs. Vet Microbiol 2015; 180:186-95. [PMID: 26390821 DOI: 10.1016/j.vetmic.2015.08.027] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2014] [Revised: 08/26/2015] [Accepted: 08/27/2015] [Indexed: 11/28/2022]
Abstract
The pathogenic role of torque teno sus virus (TTSuV) in swine is controversial among different studies. The present study intended to evaluate the potential pathogenicity of TTSuV based on its correlations with the histopathological changes, various common concurrently infected viral pathogens including porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine parvovirus (PPV), as well as changes in the distribution and population of host immunocytes such as B lymphocytes, T lymphocytes, and macrophages by using the superficial inguinal lymph nodes (siLNs) of wasting pigs. A tissue microarray consisting of 270 available siLNs collected from 262 clinically wasting and 8 healthy pigs, respectively, were used for the detection of TTSuV1, TTSuV2, PCV2, PRRSV, and PPV by either in situ hybridization (ISH) or immunohistochemical (IHC) staining, and for the detection of various subsets of immunocytes by IHC staining with monoclonal antibodies to CD3, CD79a, and lysozyme. The slides were then subject to digital scanning followed by a semi-quantitative positive pixel evaluation for further statistical analysis. Although a high prevalence of TTSuV1 and/or TTSuV2 infection was noted in both wasting and healthy pigs, the wasting pigs had a significantly higher intensity in both TTSuV1 and TTSuV2 ISH-positive signals than healthy ones did. In the wasting pigs, a significant positive correlation in the tissue viral load was noted between TTSuV1 and TTSuV2 and between TTSuV2 and PCV2, but not between TTSuV1 and PCV2. Conversely, a significant negative correlation in the tissue viral load was revealed between TTSuV2, but not TTSuV1, and PRRSV. The tissue viral load of TTSuV1 was significantly correlated with B cell hyperplasia, while the tissue viral load of TTSuV2 was significantly correlated with increased macrophage population. The ISH positivity of TTSuV2 was significantly correlated with lymphoid depletion and granulomatous inflammation, which are the characteristic histopathological findings in postweaning multisystemic wasting syndrome-affected pigs. These findings suggest that both TTSuV species may have the potential involving the development of porcine circovirus-associated lymphoid lesions via alternating the host immune system.
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Affiliation(s)
- Yao Lee
- Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan, ROC; Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
| | - Chun-Ming Lin
- Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan, ROC
| | - Chian-Ren Jeng
- Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan, ROC
| | - Hui-Wen Chang
- Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan, ROC
| | - Chih-Cheng Chang
- Department of Veterinary Medicine, National Chiayi University, Chiayi 60054, Taiwan, ROC.
| | - Victor Fei Pang
- Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Taipei 10617, Taiwan, ROC.
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Complete genome sequences of novel anelloviruses from laboratory rats. GENOME ANNOUNCEMENTS 2015; 3:3/1/e01262-14. [PMID: 25657264 PMCID: PMC4319603 DOI: 10.1128/genomea.01262-14] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Anelloviruses are nonenveloped single-stranded DNA viruses infecting a wide range of mammals. We report three complete genomes of novel anelloviruses detected in laboratory rats. Phylogenetic analysis demonstrates that these viruses are related to but distinct from recently described rodent Torque teno viruses (RoTTVs) found in wild rodent species.
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Nishiyama S, Dutia BM, Stewart JP, Meredith AL, Shaw DJ, Simmonds P, Sharp CP. Identification of novel anelloviruses with broad diversity in UK rodents. J Gen Virol 2014; 95:1544-1553. [PMID: 24744300 PMCID: PMC4059270 DOI: 10.1099/vir.0.065219-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Anelloviruses are a family of small circular ssDNA viruses with a vast genetic diversity. Human infections with the prototype anellovirus, torque teno virus (TTV), are ubiquitous and related viruses have been described in a number of other mammalian hosts. Despite over 15 years of investigation, there is still little known about the pathogenesis and possible disease associations of anellovirus infections, arising in part due to the lack of a robust cell culture system for viral replication or tractable small-animal model. We report the identification of diverse anelloviruses in several species of wild rodents. The viruses are highly prevalent in wood mice (Apodemus sylvaticus) and field voles (Microtus agrestis), detectable at a low frequency in bank voles (Myodes glareolus), but absent from house mice (Mus musculus). The viruses identified have a genomic organization consistent with other anelloviruses, but form two clear phylogenetic groups that are as distinct from each other as from defined genera.
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Affiliation(s)
- Shoko Nishiyama
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
| | - Bernadette M Dutia
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
| | - James P Stewart
- Department of Infection Biology, University of Liverpool, Liverpool Science Park, 146 Brownlow Hill, Liverpool L3 5RF, UK
| | - Anna L Meredith
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
| | - Darren J Shaw
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
| | - Peter Simmonds
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
| | - Colin P Sharp
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
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Lin J, Ganesh A. Water quality indicators: bacteria, coliphages, enteric viruses. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2013; 23:484-506. [PMID: 23438312 DOI: 10.1080/09603123.2013.769201] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Water quality through the presence of pathogenic enteric microorganisms may affect human health. Coliform bacteria, Escherichia coli and coliphages are normally used as indicators of water quality. However, the presence of above-mentioned indicators do not always suggest the presence of human enteric viruses. It is important to study human enteric viruses in water. Human enteric viruses can tolerate fluctuating environmental conditions and survive in the environment for long periods of time becoming causal agents of diarrhoeal diseases. Therefore, the potential of human pathogenic viruses as significant indicators of water quality is emerging. Human Adenoviruses and other viruses have been proposed as suitable indices for the effective identification of such organisms of human origin contaminating water systems. This article reports on the recent developments in the management of water quality specifically focusing on human enteric viruses as indicators.
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Affiliation(s)
- Johnson Lin
- a School of Life Sciences , University of KwaZulu-Natal , Durban , South Africa
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Mancuso R, Saresella M, Hernis A, Agostini S, Piancone F, Caputo D, Maggi F, Clerici M. Torque teno virus (TTV) in multiple sclerosis patients with different patterns of disease. J Med Virol 2013; 85:2176-83. [DOI: 10.1002/jmv.23707] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2013] [Indexed: 12/20/2022]
Affiliation(s)
| | | | | | - Simone Agostini
- Don C. Gnocchi Foundation; ONLUS; Milan Italy
- Department of Physiopathology and Transplantation; University of Milan; Milan Italy
| | - Federica Piancone
- Don C. Gnocchi Foundation; ONLUS; Milan Italy
- Department of Physiopathology and Transplantation; University of Milan; Milan Italy
| | | | - Fabrizio Maggi
- Department of Translational Research and New Technologies in Medicine and Surgery, Virology Unit; Pisa University Hospital (AOUP); University of Pisa; Pisa Italy
| | - Mario Clerici
- Don C. Gnocchi Foundation; ONLUS; Milan Italy
- Department of Physiopathology and Transplantation; University of Milan; Milan Italy
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12
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Increased prevalence of anellovirus in pediatric patients with fever. PLoS One 2012; 7:e50937. [PMID: 23226428 PMCID: PMC3511395 DOI: 10.1371/journal.pone.0050937] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2012] [Accepted: 10/25/2012] [Indexed: 01/03/2023] Open
Abstract
The Anelloviridae family consists of non-enveloped, circular, single-stranded DNA viruses. Three genera of anellovirus are known to infect humans, named TTV, TTMDV, and TTMV. Although anelloviruses were initially thought to cause non-A-G viral hepatitis, continued research has shown no definitive associations between anellovirus and human disease to date. Using high-throughput sequencing, we investigated the association between anelloviruses and fever in pediatric patients 2–36 months of age. We determined that although anelloviruses were present in a large number of specimens from both febrile and afebrile patients, they were more prevalent in the plasma and nasopharyngeal (NP) specimens of febrile patients compared to afebrile controls. Using PCR to detect each of the three species of anellovirus that infect humans, we found that anellovirus species TTV and TTMDV were more prevalent in the plasma and NP specimens of febrile patients compared to afebrile controls. This was not the case for species TTMV which was found in similar percentages of febrile and afebrile patient specimens. Analysis of patient age showed that the percentage of plasma and NP specimens containing anellovirus increased with age until patients were 19–24 months of age, after which the percentage of anellovirus positive patient specimens dropped. This trend was striking for TTV and TTMDV and very modest for TTMV in both plasma and NP specimens. Finally, as the temperature of febrile patients increased, so too did the frequency of TTV and TTMDV detection. Again, TTMV was equally present in both febrile and afebrile patient specimens. Taken together these data indicate that the human anellovirus species TTV and TTMDV are associated with fever in children, while the highly related human anellovirus TTMV has no association with fever.
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13
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Chen T, Väisänen E, Mattila PS, Hedman K, Söderlund-Venermo M. Antigenic diversity and seroprevalences of Torque teno viruses in children and adults by ORF2-based immunoassays. J Gen Virol 2012; 94:409-417. [PMID: 23114629 DOI: 10.1099/vir.0.046862-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Torque teno viruses (TTVs) circulate widely among humans, causing persistent viraemia in healthy individuals. Numerous TTV isolates with high genetic variability have been identified and segregated into 29 species of five major phylogenetic groups. To date, the diversity of TTV sequences, challenges in protein expression and the subsequent lack of serological assays have hampered TTV seroprevalence studies. Moreover, the antigenic relationships of different TTVs and their specific seroprevalences in humans remain unknown. For five TTV strains--belonging to different species of four genogroups--we developed, using recombinant glutathione S-transferase (GST)-fused TTV ORF2 proteins, glutathione-GST capture enzyme immunoassays (EIAs) detecting antibodies towards conformational epitopes. We then analysed serum samples from 178 healthy adults and 108 children; IgG reactivities were observed either towards a single strain or towards multiple strains, which pointed to antigenic distinction of TTV species. The overall seroprevalence for the five TTVs peaked at 43 % (18 of 42) in children 2-4 years of age, subsequently declined, and again reached 42 % (74 of 178) among adults. TTV6 species-specific IgG predominated in children, whereas that for TTV13 predominated in adults. During a 3 year follow-up of the same children, both species-specific seroconversions and seroreversions occurred. This is the first EIA-based study of different TTVs, providing a new approach for seroepidemiology and diagnosis of TTV infections. Our data suggest that different TTVs in humans may differ in antiviral antibody profiles, infection patterns and epidemiology.
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Affiliation(s)
- Tingting Chen
- Department of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland
| | - Elina Väisänen
- Department of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland
| | - Petri S Mattila
- Department of Otorhinolaryngology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
| | - Klaus Hedman
- Department of Virology and Immunology, Helsinki University Central Hospital Laboratory Division, Helsinki, Finland.,Department of Virology, Haartman Institute, University of Helsinki, Helsinki, Finland
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14
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Zhang Z, Wang Y, Fan H, Lu C. Natural infection with torque teno sus virus 1 (TTSuV1) suppresses the immune response to porcine reproductive and respiratory syndrome virus (PRRSV) vaccination. Arch Virol 2012; 157:927-33. [PMID: 22327391 DOI: 10.1007/s00705-012-1249-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2011] [Accepted: 01/10/2012] [Indexed: 10/14/2022]
Abstract
To evaluate the effect of natural infection with TTSuV1 on the antibody response to vaccination with PRRS vaccine and clinical signs when co-infected with virulent PRRSV, 15 4-week-old TTSuV1-positive piglets and 20 TTSuV1-negative piglets were selected by PCR from two pig farms in Jiangsu province. TTSuV1-negative pigs were divided into four groups, and TTSuV1-positive pigs were divided into three groups. Experimental pigs were vaccinated with a PRRSV modified live virus (MLV) at 6 weeks of age and subsequently challenged with a virulent strain of PRRSV at 10 weeks of age. A TTSuV1-negative control group and an unvaccinated PRRS MLV control group were tested at the same time. The levels of antibody/cytokine and protective efficiency against PRRS MLV vaccine were evaluated. TTSuV1-infected/PRRSV-vaccinated pigs had lower levels of PRRSV antibody, as well as IFN-γ, IL-10 and T lymphocyte proliferation, than the TTSuV1-uninfected/PRRSV-vaccinated group (P < 0.05, except IL-10) after vaccination at only one time point. TTSuV1-infected/PRRS MLV-vaccinated/PRRSV-challenged pigs had more severe clinical signs (P > 0.05), more macroscopic lung lesions (P < 0.05) and lower levels of PRRSV antibody (P < 0.05 at 7 to 14 days post-PRRSV-challenge) than TTSuV1-uninfected/PRRSV-vaccinated/PRRSV-challenged pigs. These data indicate that TTSuV1 natural infection has an adverse effect on the development of host immune responses, suppresses immunization by the PRRS MLV vaccine, and exacerbates PRRS to a certain extent in pigs.
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Affiliation(s)
- Zhicheng Zhang
- Key Lab of Animal Bacteriology, Ministry of Agriculture, Nanjing Agricultural University, Nanjing 210095, China
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15
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Kakalacheva K, Münz C, Lünemann JD. Viral triggers of multiple sclerosis. Biochim Biophys Acta Mol Basis Dis 2010; 1812:132-40. [PMID: 20600868 PMCID: PMC7126972 DOI: 10.1016/j.bbadis.2010.06.012] [Citation(s) in RCA: 84] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2009] [Revised: 06/04/2010] [Accepted: 06/16/2010] [Indexed: 01/19/2023]
Abstract
Genetic and environmental factors jointly determine the susceptibility to develop Multiple Sclerosis (MS). Collaborative efforts during the past years achieved substantial progress in defining the genetic architecture, underlying susceptibility to MS. Similar to other autoimmune diseases, HLA-DR and HLA-DQ alleles within the HLA class II region on chromosome 6p21 are the highest-risk-conferring genes. Less-robust susceptibility effects have been identified for MHC class I alleles and for non-MHC regions. The role of environmental risk factors and their interaction with genetic susceptibility alleles are much less well defined, despite the fact that infections have long been associated with MS development. Current data suggest that infectious triggers are most likely ubiquitous, i.e., highly prevalent in the general population, and that they require a permissive genetic trait which predisposes for MS development. In this review article, we illustrate mechanisms of infection-induced immunopathologies in experimental animal models of autoimmune CNS inflammation, discuss challenges for the translation of these experimental data into human immunology research, and provide future perspectives on how novel model systems could be utilized to better define the role of viral pathogens in MS.
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Aramouni M, Segalés J, Cortey M, Kekarainen T. Age-related tissue distribution of swine Torque teno sus virus 1 and 2. Vet Microbiol 2010; 146:350-3. [PMID: 20646878 DOI: 10.1016/j.vetmic.2010.05.036] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2010] [Revised: 05/15/2010] [Accepted: 05/21/2010] [Indexed: 11/19/2022]
Abstract
Torque teno viruses (TTVs) are small, non-enveloped viruses with a circular single-stranded DNA genome, belonging to the family Anelloviridae. In swine, two genetically distinct species have been identified, Torque teno sus virus 1 (TTSuV1) and 2 (TTSuV2). The aim of the present work was to study the tissue distribution of TTSuV1 and TTSuV2 in pigs of different ages, including foetuses at the second and last thirds of gestation, and animals at 5 days and 5, 15 and 24 weeks of age. Investigated tissues included brain, lung, mediastinal and mesenteric lymph nodes, heart, liver, spleen, kidney and bone marrow. Viral DNA from tissue extractions were tested by a comparative PCR for the presence of TTSuVs. Overall, TTSuV1 and TTSuV2 species were found in all tissues tested, with variations depending on age, and following similar infection dynamics in all tissues, increasing progressively in prevalence and virus load over time. The highest prevalence was found at 5 weeks of age and maintained afterwards, and the highest loads of virus in the different tissues were seen in the oldest animals (15 and 24 weeks of age). No animals were negative to TTV, including foetuses. In conclusion, the present study indicated that swine TTSuV1 and TTSuV2 can be found virtually in all body tissues of the pig. Both swine TTV species were present in high levels in almost all older animals, while viral negative tissues were only found in 5-week-old and 5-day-old pigs, and foetuses.
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Affiliation(s)
- M Aramouni
- Centre de Recerca en Sanitat Animal (CReSA), UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
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Ellis JA, Allan G, Krakowka S. Effect of coinfection with genogroup 1 porcine torque teno virus on porcine circovirus type 2-associated postweaning multisystemic wasting syndrome in gnotobiotic pigs. Am J Vet Res 2009; 69:1608-14. [PMID: 19046008 DOI: 10.2460/ajvr.69.12.1608] [Citation(s) in RCA: 108] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To determine whether genogroup 1 porcine torque teno virus (g1-TTV) can potentiate clinical disease associated with porcine circovirus type 2 (PCV2). SAMPLE POPULATION 33 gnotobiotic baby pigs. PROCEDURES Pigs were allocated into 7 groups: group A, 5 uninoculated control pigs from 3 litters; group B, 4 pigs oronasally inoculated with PCV2 alone; group C, 4 pigs inoculated IP with first-passage g1-TTV alone; group D, 4 pigs inoculated IP with fourth-passage g1-TTV alone; group E, 6 pigs inoculated IP with first-passage g1-TTV and then oronasally inoculated with PCV2 7 days later; group F, 6 pigs inoculated IP with fourth-passage g1-TTV and then inoculated oronasally with PCV2 7 days later; and group G, 4 pigs inoculated oro-nasally with PCV2 and then inoculated IP with fourth-passage g1-TTV 7 days later. RESULTS 6 of 12 pigs inoculated with g1-TTV prior to PCV2 developed acute onset of postweaning multisystemic wasting syndrome (PMWS). None of the pigs inoculated with g1-TTV alone or PCV2 alone or that were challenge exposed to g1-TTV after establishment of infection with PCV2 developed clinical illness. Uninoculated control pigs remained healthy. CONCLUSIONS AND CLINICAL RELEVANCE These data implicated g1-TTV as another viral infection that facilitates PCV2-induced PMWS. This raises the possibility that torque teno viruses in swine may contribute to disease expression currently associated with only a single infectious agent.
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Affiliation(s)
- John A Ellis
- Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
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Krakowka S, Ellis JA. Evaluation of the effects of porcine genogroup 1 torque teno virus in gnotobiotic swine. Am J Vet Res 2009; 69:1623-9. [PMID: 19046010 DOI: 10.2460/ajvr.69.12.1623] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To determine whether porcine genogroup 1 torque teno virus (g1-TTV) can infect and cause disease in gnotobiotic swine. SAMPLE POPULATION 20 conventional baby pigs and 46 gnotobiotic baby pigs. PROCEDURES Porcine g1-TTV was transmitted from conventional swine to gnotobiotic pigs via pooled leukocyte-rich plasmas (n=18) that had positive results for g1-TTV DNA. Bone marrow-liver homogenates that had positive results for torque teno virus (TTV) were used in 4 serial passages in gnotobiotic pigs (2 pigs/passage). A pathogenesis experiment was conducted with in vivo passages of g1-TTV in various groups of gnotobiotic pigs. RESULTS All g1-TTV inoculated pigs had no clinical signs but developed interstitial pneumonia, transient thymic atrophy, membranous glomerulonephropathy, and modest lymphocytic to histiocytic infiltrates in the liver after inoculation with the TTV-containing tissue homogenate; these changes were not detected in uninoculated control pigs or pigs injected with tissue homogenate devoid of TTV DNAs. In situ hybridization was used to identify g1-TTV DNAs in bone marrow mononuclear cells. CONCLUSIONS AND CLINICAL RELEVANCE Analysis of these data revealed that porcine g1-TTV was readily transmitted to TTV-naïve swine and that infection was associated with characteristic pathologic changes in gnotobiotic pigs inoculated with g1-TTV. Thus, g1-TTV could be an unrecognized pathogenic viral infectious agent of swine. This indicated a directly associated induction of lesions attributable to TTV infection in swine for a virus of the genus Anellovirus.
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Affiliation(s)
- Steven Krakowka
- Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA
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In utero transmission of porcine torque teno viruses. Vet Microbiol 2009; 137:375-9. [DOI: 10.1016/j.vetmic.2009.02.001] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2008] [Revised: 01/20/2009] [Accepted: 02/03/2009] [Indexed: 11/17/2022]
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Ninomiya M, Takahashi M, Hoshino Y, Ichiyama K, Simmonds P, Okamoto H. Analysis of the entire genomes of torque teno midi virus variants in chimpanzees: infrequent cross-species infection between humans and chimpanzees. J Gen Virol 2009; 90:347-358. [PMID: 19141443 DOI: 10.1099/vir.0.007385-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Humans are frequently infected with three anelloviruses which have circular DNA genomes of 3.6-3.9 kb [Torque teno virus (TTV)], 2.8-2.9 kb [Torque teno mini virus (TTMV)] and 3.2 kb [a recently discovered anellovirus named Torque teno midi virus (TTMDV)]. Unexpectedly, human TTMDV DNA was not detectable in any of 74 chimpanzees tested, although all but one tested positive for both human TTV and TTMV DNA. Using universal primers for anelloviruses, novel variants of TTMDV that are phylogenetically clearly separate from human TTMDV were identified from chimpanzees, and over the entire genome, three chimpanzee TTMDV variants differed by 17.9-20.3 % from each other and by 40.4-43.6 % from all 18 reported human TTMDVs. A newly developed PCR assay that uses chimpanzee TTMDV-specific primers revealed the high prevalence of chimpanzee TTMDV in chimpanzees (63/74, 85 %) but low prevalence in humans (1/100). While variants of TTV and TTMV from chimpanzees and humans were phylogenetically interspersed, those of TTMDV were monophyletic for each species, with sequence diversity of <33 and <20 % within the 18 human and three chimpanzee TTMDV variants, respectively. Maximum within-group divergence values for TTV and TTMV were 51 and 57 %, respectively; both of these values were substantially greater than the maximum divergence among TTMDV variants (44 %), consistent with a later evolutionary emergence of TTMDV. However, substantiation of this hypothesis will require further analysis of genetic diversity using an expanded dataset of TTMDV variants in humans and chimpanzees. Similarly, the underlying mechanism of observed infrequent cross-species infection of TTMDV between humans and chimpanzees deserves further analysis.
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Affiliation(s)
- Masashi Ninomiya
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi-Ken 329-0498, Japan
| | - Masaharu Takahashi
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi-Ken 329-0498, Japan
| | - Yu Hoshino
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi-Ken 329-0498, Japan
| | - Koji Ichiyama
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi-Ken 329-0498, Japan
| | - Peter Simmonds
- Virus Evolution Group, Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK
| | - Hiroaki Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, Tochigi-Ken 329-0498, Japan
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Abstract
Since 1997, groups of novel nonenveloped DNA viruses with a circular, single-stranded (negative sense) DNA genome of 3.6-3.9 kb, 3.2 kb, or 2.8-2.9 kb in size have been discovered and designated Torque teno virus (TTV), Torque teno midi virus (TTMDV), and Torque teno mini virus (TTMV), respectively, in the floating genus Anellovirus. These three anelloviruses frequently and ubiquitously infect humans, and the infections are characterized by lifelong viremia and great genetic variability. Although TTV infection has been epidemiologically suggested to be associated with many diseases including liver diseases, respiratory disorders, hematological disorders, and cancer, there is no direct causal evidence for links between TTV infection and specific clinical diseases. The pathogenetic role of TTMV and TTMDV infections remains unknown. The changing ratio of the three anelloviruses to each other over time, relative viral load, or combination of different genotype(s) of each anellovirus may be associated with the pathogenicity or the disease-inducing potential of these three human anelloviruses. To clarify their disease association, polymerase chain reaction (PCR) systems for accurately detecting, differentiating, and quantitating all of the genotypes and/or genogroups of TTV, TTMDV, and TTMV should be established and standardized, as should methods to detect past infections and immunological responses to anellovirus infections.
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Affiliation(s)
- H Okamoto
- Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke-Shi, Tochigi-Ken 329-0498, Japan.
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Les anellovirus (TTV et variants) : données actuelles dix ans après leur découverte. Transfus Clin Biol 2008; 15:406-15. [DOI: 10.1016/j.tracli.2008.10.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2008] [Accepted: 10/10/2008] [Indexed: 11/21/2022]
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Krakowka S, Ringler SS, Arumugam P, McKillen J, McIntosh K, Hartunian C, Hamberg A, Rings M, Allan G, Ellis JA. Evaluation ofMycoplasma hyopneumoniaebacterins for porcine torque teno virus DNAs. Am J Vet Res 2008; 69:1601-7. [DOI: 10.2460/ajvr.69.12.1601] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Kakkola L, Bondén H, Hedman L, Kivi N, Moisala S, Julin J, Ylä-Liedenpohja J, Miettinen S, Kantola K, Hedman K, Söderlund-Venermo M. Expression of all six human Torque teno virus (TTV) proteins in bacteria and in insect cells, and analysis of their IgG responses. Virology 2008; 382:182-9. [PMID: 18947848 DOI: 10.1016/j.virol.2008.09.012] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2008] [Revised: 07/21/2008] [Accepted: 09/08/2008] [Indexed: 01/03/2023]
Abstract
Torque teno virus (TTV) is a non-enveloped human virus with a circular ( approximately 3800 nt) ssDNA genome. TTV transcription results in three viral mRNAs and six proteins, the function or antigenicity of which are unknown. The six open reading frames of TTV genotype 6 were expressed in bacteria and insect cells. Expression of the ORF1/1-encoded protein was inefficient, while expression of the others was successful, with ORF1 and ORF1/2 as arginine-rich region depleted. All six recombinant TTV proteins were antigenic. Of healthy adults, 11/25 (44%) showed strong IgG reactivity with one or more proteins. Four subjects, two of whom were genotype-6-DNA positive, were followed. One of the latter showed concurrently a strong IgG response against the ORF1 protein. The other showed appearance of IgG against the ORF2 protein concomitantly with resolution of the genotype-6 viremia. The genotype-6 sequences remained unaltered for years, suggesting that some mechanisms other than amino acid substitutions play a role in TTV immune evasion.
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Affiliation(s)
- Laura Kakkola
- Department of Virology, Haartman Institute and Helsinki University Central Hospital Laboratory, Haartmaninkatu 3, P.O. Box 21, University of Helsinki, FIN-00014, Finland.
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25
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Griffin JS, Plummer JD, Long SC. Torque teno virus: an improved indicator for viral pathogens in drinking waters. Virol J 2008; 5:112. [PMID: 18834517 PMCID: PMC2569923 DOI: 10.1186/1743-422x-5-112] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2008] [Accepted: 10/03/2008] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Currently applied indicator organism systems, such as coliforms, are not fully protective of public health from enteric viruses in water sources. Waterborne disease outbreaks have occurred in systems that tested negative for coliforms, and positive coliform results do not necessarily correlate with viral risk. It is widely recognized that bacterial indicators do not co-occur exclusively with infectious viruses, nor do they respond in the same manner to environmental or engineered stressors. Thus, a more appropriate indicator of health risks from infectious enteric viruses is needed. PRESENTATION OF THE HYPOTHESIS Torque teno virus is a small, non-enveloped DNA virus that likely exhibits similar transport characteristics to pathogenic enteric viruses. Torque teno virus is unique among enteric viral pathogens in that it appears to be ubiquitous in humans, elicits seemingly innocuous infections, and does not exhibit seasonal fluctuations or epidemic spikes. Torque teno virus is transmitted primarily via the fecal-oral route and can be assayed using rapid molecular techniques. We hypothesize that Torque teno virus is a more appropriate indicator of viral pathogens in drinking waters than currently used indicator systems based solely on bacteria. TESTING THE HYPOTHESIS To test the hypothesis, a multi-phased research approach is needed. First, a reliable Torque teno virus assay must be developed. A rapid, sensitive, and specific PCR method using established nested primer sets would be most appropriate for routine monitoring of waters. Because PCR detects both infectious and inactivated virus, an in vitro method to assess infectivity also is needed. The density and occurrence of Torque teno virus in feces, wastewater, and source waters must be established to define spatial and temporal stability of this potential indicator. Finally, Torque teno virus behavior through drinking water treatment plants must be determined with co-assessment of traditional indicators and enteric viral pathogens to assess whether correlations exist. IMPLICATIONS OF THE HYPOTHESIS If substantiated, Torque teno virus could provide a completely new, reliable, and efficient indicator system for viral pathogen risk. This indicator would have broad application to drinking water utilities, watershed managers, and protection agencies and would provide a better means to assess viral risk and protect public health.
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Affiliation(s)
- Jennifer S Griffin
- Department of Civil and Environmental Engineering, 100 Institute Road, Worcester Polytechnic Institute, Worcester, MA 01609, USA
| | - Jeanine D Plummer
- Department of Civil and Environmental Engineering, 100 Institute Road, Worcester Polytechnic Institute, Worcester, MA 01609, USA
| | - Sharon C Long
- Department of Soil Science and Wisconsin State Laboratory of Hygiene, 2601 Agriculture Drive, Madison, WI 53718, USA
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Welch J, Bienek C, Gomperts E, Simmonds P. Resistance of porcine circovirus and chicken anemia virus to virus inactivation procedures used for blood products. Transfusion 2006; 46:1951-8. [PMID: 17076851 DOI: 10.1111/j.1537-2995.2006.01003.x] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Virus inactivation procedures are used to prevent contamination of plasma-derived blood products with viruses. Pasteurization or prolonged dry heat has proven effective against several enveloped and nonenveloped viruses and provides an additional layer of safety for plasma products. STUDY DESIGN AND METHODS The resistance of porcine circovirus 2 (PCV2) and chicken anemia virus (CAV), two small, nonenveloped viruses, to standard (pasteurization, 10 hr at 60 degrees C; dry heating, 80 degrees C for 72 hr) and more extreme heat inactivation procedures (temperatures up to 120 degrees C) was determined. The ability of these procedures to inactivate PCV2 and CAV was measured by comparison of in vitro infectivity before and after treatment. RESULTS Infectivity of PCV2 and CAV was reduced by approximately 1.6 and 1.4 log by pasteurization and by 0.75 and 1.25 log by dry-heat treatment, both substantially more resistant than other viruses previously investigated. PCV2 and CAV were additionally almost completely resistant to dry-heat treatment up to 120 degrees C for 30 minutes (mean log infectivity reductions, 1.25 and 0.6), although both were more effectively inactivated when the temperature of wet-heat treatment was increased to 80 degrees C (>3.2 and >3.6 log infectivity reduction). CONCLUSION Although neither PCV2 nor CAV are known to infect humans, their inactivation properties may represent those of other small DNA viruses known to be present (e.g., TT virus, small anellovirus) or potentially present in human plasma. Findings of extreme thermal resistance demonstrate that recipients of plasma-derived therapeutics may potentially still be exposed to small DNA viruses, despite the implementation of viral inactivation steps.
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Affiliation(s)
- Jon Welch
- Virus Evolution Group, Center for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, UK
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27
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Al-Mozaini MA, Al-Ahdal MN, Kessie G, Dela Cruz DM, Rezeig MA, Al-Shammary FJ. Molecular epidemiology and genotyping of TT virus isolated from Saudi blood donors and hepatitis patients. Ann Saudi Med 2006; 26:444-9. [PMID: 17143020 PMCID: PMC6074335 DOI: 10.5144/0256-4947.2006.444] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND In Saudi Arabia, the epidemiology and clinical significance of Torque Teno virus (TTV) infection alone and in patients with hepatitis virus infections have not been determined in a single study. In this paper, we molecularly investigated the rate and genotypes of TTV infection among Saudi Arabian blood donors and patients with viral hepatitis. The effect of TTV coinfection on viral hepatitis was also examined. SUBJECTS AND METHODS DNA was extracted from the sera of 200 healthy blood volunteers, 45 hepatitis B virus patients, 100 hepatitis C virus patients, 19 hepatitis G virus patients, and 56 non-A-G hepatitis patients. TTV DNA was amplified using primers derived from the ORF1 and 5'UTR regions. The alanine aminotransferase (ALT) level was determined for each specimen. Sequencing of ORF1 amplicons was carried out to investigate TTV genotypes. RESULTS Using primers derived from ORF1 and 5'UTR, TTV DNA was detected in 5.5% and 50.5%, respectively, of healthy blood donors, in 2.2% and 88.8% in hepatitis B patients, in 2.0% and 70% of hepatitis C patients, in 15.8% and 100% of hepatitis G patients, in 5.4% and 12.5% of non-A-G hepatitis patients and in 4.8% and 56.4% overall. No detrimental effect of TTV coinfection in viral hepatitis patients was noted. An overall prevalence of 4.8% and 56.4% was established. Phylogenetic analysis indicated that the most common genotype of TTV among Saudis is 2c. CONCLUSION The rate of TTV infection among Saudi Arabians seems to be lower than that stated in previous reports on Saudi Arabia and in some other countries. The virus does not seem to worsen the status of those who are suffering from viral hepatitis infection.
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Affiliation(s)
- Maha A. Al-Mozaini
- Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Mohammed N. Al-Ahdal
- Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - George Kessie
- Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Damian M. Dela Cruz
- Department of Biological and Medical Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Mohammed A. Rezeig
- Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Fahad J. Al-Shammary
- Department of Clinical Laboratory Sciences. College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
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Spataro P, Di Pietro A, Scoglio ME, Visalli G, Chirico C, Picerno I, Ferlazzo N, Campo S, Bellinghieri G, Savica V, Santoro D, Buemi M, Costantino F. Prevalence of SENV-H and SENV-D virus: epidemiological study in blood donors and dialysis patients. Ren Fail 2006; 28:441-8. [PMID: 16825095 DOI: 10.1080/08860220600684225] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
INTRODUCTION Recently, the identification of the SEN virus as a possible etiological agent of parental transmission hepatitis led to the study of the prevalence of such pathogen agents, particularly SENV-H, in our population. This paper compares the rate prevalence in high-risk subjects, such as dialysis patients, and low-risk subjects, such as blood donors. MATERIAL AND METHODS The study was carried out on SEN virus DNA extracted from serum of dialysis patients and blood donors, and the presence of viral genomes was performed by the nested PCR method. RESULTS The results showed a higher prevalence in male blood donors, supporting the hypothesis of an epidemiological role for sexual and also parental transmission, as is clearly demonstrated by the high prevalence in dialysis patients. The result reduced the importance of the possible etiological role of the SEN virus due to the high percentage of positivity in healthy population, and it induces one to consider poorly significant the pathogenicity of such viral agents. CONCLUSION For this instance, the authors, in agreement with the phylogenically related TT virus, described SEN viruses as absolutely not pathogens and considered them as "simple guests."
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Affiliation(s)
- Pasquale Spataro
- Department of Hygiene, Preventive Medicine, and Public Health, University of Messina, Italy
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Irshad M, Joshi YK, Sharma Y, Dhar I. Transfusion transmitted virus: A review on its molecular characteristics and role in medicine. World J Gastroenterol 2006; 12:5122-5134. [PMID: 16937521 PMCID: PMC4088008 DOI: 10.3748/wjg.v12.i32.5122] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2006] [Revised: 05/15/2006] [Accepted: 05/22/2006] [Indexed: 02/06/2023] Open
Abstract
The present review gives an updated overview of transfusion transmitted virus (TTV), a novel agent, in relation to its molecular characteristics, epidemiological features, modes of transmission, tissue tropism, pathogenesis, role in various diseases and its eradication from the body. TTV, a DNA virus, is a single stranded, non-enveloped, 3.8 kb long DNA virus with a small and covalently closed circular genome comprising 3852 bases. It was tentatively designated Circinoviridae virus. TTV genome sequence is heterogeneous and reveals the existence of six different genotypes and several subtypes. TTV has been reported to transmit not only via parenteral routes, but also via alternate routes. This virus has been detected in different non-human primates as well. At present, TTV is detected by polymerase chain reaction (PCR) with no other available diagnostic assays. It shows its presence globally and was detected in high percent populations of healthy persons as well as in various disease groups. Initially it was supposed to have strong association with liver disease; however, there is little evidence to show its liver tropism and contribution in causing liver diseases. It shows high prevalence in hemodialysis patients, pointing towards its significance in renal diseases. In addition, TTV is associated with several infectious and non-infectious diseases. Though, its exact pathogenesis is not yet clear, TTV virus possibly resides and multiplies in bone marrow cells and peripheral blood mononuclear cells (PBMCs). Recently, attempts have been made to eradicate this virus with interferon treatment. More information is still needed to extricate various mysteries related to TTV.
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Affiliation(s)
- M Irshad
- Clinical Biochemistry Division, Department of Laboratory Medicine, PO Box -4938, A I I M S, New Delhi-110029, India.
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Huang LR, Wang HH, Lin WS, Lin CL. The prevalence of SEN virus infection in blood donors in Taiwan. J Infect 2005; 51:30-4. [PMID: 15979487 DOI: 10.1016/j.jinf.2005.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2004] [Accepted: 03/03/2005] [Indexed: 01/14/2023]
Abstract
OBJECTIVES To determine the prevalence of SENV infections among blood donors in central Taiwan and to clarify the relationship between these infections and elevated alanine aminotransaminase (ALT) values. METHODS DNA was extracted from plasma of 200 blood donors and amplified by seminested PCR. RESULTS For all donors, the prevalence of SENV-D was 32%, and of SENV-H was 30.5%. Prevalence of mixed SENV-D/H infection was 11.5% and of SENV-D and/or SENV-H (SENV-D/H) was 51%. Infections were not associated with age, gender, or raised ALT values. CONCLUSIONS SENV-D and SENV-H infections are common among blood donors in central Taiwan but are unlikely to contribute to abnormal ALT values.
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Affiliation(s)
- Lan-Ru Huang
- Department of Medical Technology, Chungtai Institute of Health Sciences and Technology, Taichung, Taiwan, ROC.
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Saláková M, Němeček V, König J, Tachezy R. Age-specific prevalence, transmission and phylogeny of TT virus in the Czech Republic. BMC Infect Dis 2004; 4:56. [PMID: 15575965 PMCID: PMC539280 DOI: 10.1186/1471-2334-4-56] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2004] [Accepted: 12/03/2004] [Indexed: 11/18/2022] Open
Abstract
Background TT virus is prevalent worldwide, but its prevalence and genotype distribution in Central and East-Europe has not been determined. The high prevalence of TTV in multiply-transfused patients points to the importance of a parenteral mode of transmission, but since more than half of the general population is infected other possible routes of transmission must be considered. Methods In our study, we investigated the epidemiology, transmission and phylogeny of TTV in the Czech Republic. The following groups were selected: a control group of 196 blood donors, 20 patients with hemophilia, 49 intravenous drug users, 100 sex workers, 50 penitentiary prisoners, 208 healthy children aged 1 to 14 years, 54 cord blood samples, 52 patients with non-A-E hepatitis, 74 patients with hepatitis C, and 51 blood donors with increased ALT levels. Primers specific for the non-coding region were used. The genotype distribution was studied in 70 TTV-positive samples. Results The prevalence rate of TTV among the Czech population was 52.6%. We have shown that TTV is not transmitted prenatally. Children were infected after birth with two peaks: one at the age of two years and the other after the beginning of primary school. Adults have shown a further increase in the TTV prevalence with age. The highest TTV prevalence was found in the group of patients who had received multiple blood transfusions. The TTV prevalence rate in subjects at an increased risk of sexual transmission was not significantly higher than in the general population. Genotypes G2 and G1 were most prevalent among the Czech population, followed by G8 and G3. The subjects positive for markers of HBV and/or HCV infection tested significantly more often TTV DNA positive, which is suggestive of a common route of transmission of these three infections. Conclusions This study on TTV prevalence, mode of transmission and age-specific prevalence is the most extensive study performed in Central and Eastern Europe. It showed insights into the epidemiology of TTV infection, but failed to associate TTV infection with clinical manifestations.
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Affiliation(s)
- Martina Saláková
- Department of Experimental Virology, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic
| | - Vratislav Němeček
- National Reference Laboratory for Hepatitis, National Institute of Health, Prague, Czech Republic
| | - Jaroslav König
- National Reference Laboratory for Hepatitis, National Institute of Health, Prague, Czech Republic
| | - Ruth Tachezy
- Department of Experimental Virology, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic
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Jelcic I, Hotz-Wagenblatt A, Hunziker A, Zur Hausen H, de Villiers EM. Isolation of multiple TT virus genotypes from spleen biopsy tissue from a Hodgkin's disease patient: genome reorganization and diversity in the hypervariable region. J Virol 2004; 78:7498-507. [PMID: 15220423 PMCID: PMC434092 DOI: 10.1128/jvi.78.14.7498-7507.2004] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
We report the isolation of 24 novel genotypes of TT viruses from a surgically removed spleen of a patient with Hodgkin's disease. The sequence analysis of our 24 isolates revealed the remarkable heterogeneity of TT virus isolates not only from the same patient but also from the same biopsy material. These isolates belong to four phylogenetic groups of TT viruses. Nucleotide sequence analyses revealed five distinct genotypes (tth3, tth4, tth5, tth6, and tth7). The limited variation in sequence identity of the other isolates defines the latter as variants of four of these genotypes. A group of 6 isolates (the tth7 group) revealed a reorganization of open reading frame 1 (ORF1) leading to one larger and a varying number of smaller ORFs. The nucleotide difference of the full-length genomes was less than 1%. A variation of 69 to 97% in amino acids of a second group of 8 isolates (the tth3 group) was restricted to the hypervariable region of ORF1, indicating the existence of a quasi-species. These isolates differed by less than 2% in the remainder of their nucleotide sequences. An alignment of these isolates with 79 previously reported TT virus genotypes permits the proposal of TT virus genera and species within the family Anelloviridae in analogy to a previous proposal for the papillomaviruses (family Papillomaviridae).
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Affiliation(s)
- Ilijas Jelcic
- Division for the Characterization of Tumorviruses, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany
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Abstract
TT virus (TTV) and TTV-like mini virus (TLMV) represent the first described human circoviruses. They do not show significant sequence homology with any other animal circovirus identified to date. They are both detected with high prevalences in various body fluids. The spread mode may include the parenteral way, the transmission by saliva droplets and the fecal-oral route. Genetic variability within a viral group is high and the co-infection by distinct viral strains is common in a given individual. The description of several messenger RNAs obtained after multiple splicing revealed a specific transcription profile. Despite apparent asymptomatic infections, the possible association of variants of TTV and TLMV with a given pathology cannot be formally ruled out.
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Affiliation(s)
- Philippe Biagini
- Unité des Virus Emergents, EA 3292, Laboratoire de Virologie Moléculaire, Etablissement Français du Sang Alpes-Méditerranée et Faculté de Médecine, 149, Boulevard Baille, 13005 Marseille, France.
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Schröter M, Laufs R, Zöllner B, Knödler B, Schäfer P, Feucht HH. A novel DNA virus (SEN) among patients on maintenance hemodialysis: prevalence and clinical importance. J Clin Virol 2003; 27:69-73. [PMID: 12727531 DOI: 10.1016/s1386-6532(02)00129-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
BACKGROUND A recently discovered DNA virus (SEN) has been assumed to be responsible for posttransfusion hepatitis in humans. Phylogenetic analysis of SEN virus has revealed the existence of 8 different strains. Two of them (SEN virus strain H (SENV-H) and SENV-D) have been described as possible candidate viruses for inducing posttransfusion hepatitis. Until now, it is unclear whether patients on maintenance hemodialysis are on increased risk for acquiring SEN virus. OBJECTIVES To investigate the prevalence of SENV-H among patients on maintenance hemodialysis and to examine whether special measures have to be taken to prevent nosocomial spreading of the virus. STUDY DESIGN Serum samples derived from 78 chronically hemodialysed patients were examined for SENV-H viremia by seminested polymerase chain reaction. A panel of 226 samples from healthy blood donors served as a control group. RESULTS The prevalence of SENV-H was determined to be 12.8% (n=10) among patients on maintenance hemodialysis. This is nearly the same prevalence as in healthy blood donors (16.8%; n=38). None of the solely SENV-H-viremic individuals had clinical or biochemical signs of liver disease. Enhanced severity of liver disease could not be observed in patients coinfected with hepatitis C virus and SENV-H. CONCLUSION We conclude that SENV-H viremia is widespread among hemodialysis patients. Since no viremic patient had clinical or biochemical signs of liver disease, in our setting the hepatitis-inducing capacity of SENV-H remains unclear. On the basis of our results, at present, we do not regard it as necessary to dialyse SENV-H-viremic patients on separate machines.
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Affiliation(s)
- Matthias Schröter
- Institut für Medizinische Mikrobiologie und Immunologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, Germany.
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Thom K, Morrison C, Lewis JCM, Simmonds P. Distribution of TT virus (TTV), TTV-like minivirus, and related viruses in humans and nonhuman primates. Virology 2003; 306:324-33. [PMID: 12642105 DOI: 10.1016/s0042-6822(02)00049-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
TT virus (TTV) and TTV-like minivirus (TLMV) are small DNA viruses with single-stranded, closed circular, antisense genomes infecting man. Despite their extreme sequence heterogeneity (>50%), a highly conserved region in the untranslated region (UTR) allows both viruses to be amplified by polymerase chain reaction (PCR). TTV/TLMV infection was detected in 88 of 100 human plasma samples; amplified sequences were differentiated into TTV and TLMV by analysis of melting profiles, showing that both viruses were similarly prevalent. PCR with UTR primers also detected frequent infection with TTV/TLMV-related viruses in a wide range of apes (chimpanzees, gorillas, orangutans, gibbons) and African monkey species (mangabeys, drills, mandrills). These findings support the hypothesis for the co-evolution of TTV-like viruses with their hosts over the period of primate speciation, potentially analogous to the evolution of primate herpesviruses.
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Affiliation(s)
- K Thom
- TTI Theme Group, Scottish National Blood Transfusion Service, University of Edinburgh, Teviot Place, EH8 9AG Scotland, Edinburgh, UK
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He Z, Zhuang H, Wang X, Song S, Dong Q, Yan J, Buehring GC, Luo G. Retrospective analysis of non-A-E hepatitis: possible role of hepatitis B and C virus infection. J Med Virol 2003; 69:59-65. [PMID: 12436478 DOI: 10.1002/jmv.10248] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
In an effort to determine the cause of non-A-E hepatitis, a retrospective study was undertaken on a group of patients with hepatitis but without serological infection markers of hepatitis viruses A-E. A total of 60 patients admitted to Beijing Ditan Hospital during the period of September 1997 and September 1999 were chosen for this study. These patients were diagnosed as either acute or chronic hepatitis, but no serological markers of hepatitis viruses A-E were detected. Since TT virus (TTV), human parvovirus B19 (B19), SEN virus (SENV), and GB virus C/HGV were reported to be associated with hepatitis, attempts were made to detect the presence of these viruses in the sera of patients with non-A-E hepatitis by a nested polymerase chain reaction (nPCR) method. Also, more sensitive nPCR and RT-nPCR methods were used to determine HBV DNA and HCV RNA in these patients. Results derived from these analyses demonstrate that HBV DNA was detected in most of these patients (47/60, 78.3%), suggesting that HBV infection played a major role in occult non-A-E hepatitis and detection of HBV DNA by more sensitive PCR methods such as nPCR should be considered for diagnosis of HBV infection. In addition, HCV RNA was detected in three (5%) of these patients. However, GBV-C (HGV) RNA was not detected, and TTV, B19, and SENV appear not to be associated with non-A-E hepatitis, as the prevalence rates of these viruses in patients with non-A-E hepatitis were similar to those in patients with viral hepatitis A-E. The results from this study indicate that co-infection of TTV or B19 with HBV did not increase the severity of the disease.
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Affiliation(s)
- Zhongping He
- Research Center of Virology, Beijing Ditan Hospital, Beijing, China.
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Schröter M, Laufs R, Zöllner B, Knödler B, Schäfer P, Sterneck M, Fischer L, Feucht HH. Prevalence of SENV-H viraemia among healthy subjects and individuals at risk for parenterally transmitted diseases in Germany. J Viral Hepat 2002; 9:455-9. [PMID: 12431209 DOI: 10.1046/j.1365-2893.2002.00390.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The prevalence of a newly described DNA virus (SENV-H) was examined in a population of 599 individuals by polymerase chain reaction (PCR). All individuals were assigned to a nonrisk or a risk group depending on the presence of historical or serological factors indicating an increased risk for parenterally transmitted diseases. In a group of 226 healthy blood donors, 38 (16.8%) were found to be SENV-H viraemic. The highest prevalence of SENV-H viraemia was observed among patients infected by HIV (28 of 63; 44.4%). Contrarily, of 78 individuals on maintenance haemodialysis, only 10 (12.8%) were found positive in the SENV-H PCR. Our results demonstrate that SENV-H viraemia is widespread in the general population. Therefore, it seems to be questionable if parenteral transmission is the main route for spreading SENV-H. The hepatitis-inducing capacity of SENV-H is unclear. However, taking our clinical and epidemiological data into account it seems unlikely that this virus is responsible for hepatitis.
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Affiliation(s)
- M Schröter
- Institut für Medizinische Mikrobiologie und Immunologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
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Vasconcelos HCF, Cataldo M, Niel C. Mixed infections of adults and children with multiple TTV-like mini virus isolates. J Med Virol 2002; 68:291-8. [PMID: 12210422 DOI: 10.1002/jmv.10187] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Testing of the DNA of TTV-like mini virus (TLMV) was done with serum samples obtained from 184 patients (children and adults) who visited different outpatient clinics at a university hospital in Florianopolis, south of Brazil. TLMV DNA was detected by PCR primers from the non-coding region of the genome. A global TLMV prevalence of 78% was found (94% among children below 11 years). PCR products from three serum samples (patients A-C) were cloned, and the sequences with a length of 201-227 nucleotides were determined for 16-19 clones derived from each of the sera. Among the 16 clones derived from patient C, 15 were identical, and the remaining one had a sequence homology of 99%. In contrast, eight different sequences were obtained among the 19 clones derived from patient A, and 10 distinct sequences were depicted among the 17 clones derived from the serum of patient B. Additionally, 13 clones derived from a saliva sample of patient B were sequenced, and seven different nucleotide sequences obtained. One particular sequence was predominant in both serum (8/17 clones) and saliva (7/13 clones) of patient B. On a phylogenetic tree, sequences derived from patient A (a 6-year-old boy), as well as those derived from patient B (a 24-year-old man), were located in five distinct evolutionary branches, taking a minimum divergence of 5% between branches. This suggested that adults and children are coinfected frequently with several TLMV isolates of different origins.
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Affiliation(s)
- Helena C F Vasconcelos
- Department of Clinical Analyses, Federal University of Santa Catarina, Florianopolis, Brazil
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Kreil TR, Zimmermann K, Pable S, Schwarz HP, Dorner F. TT virus does not contaminate first-generation recombinant factor VIII concentrate. Blood 2002; 100:2271-2; author reply 2272. [PMID: 12229884 DOI: 10.1182/blood-2002-05-1584] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Abstract
OBJECTIVE To determine, in Polish blood donors, the frequency of TT virus (TTV) using different primers and the sequence diversity of TTV genotypes. MATERIALS AND METHODS Two-hundred blood donors were studied. TTV DNA was detected by the polymerase chain reaction (PCR) using primers for the coding (ORF1) and non-coding (NC) regions. Twenty isolates were genotyped by sequencing the ORF1 fragment. RESULTS TTV DNA was detected in 78% of donors using NC primers and in 10% using ORF1 primers. The frequency of TTV DNA detection by NC primers was observed to increase with donor age, whereas the frequency of detection by ORF primers did not differ between various age-groups. The nucleotide sequence homology of Polish TTV isolates ranged from 59 to 99%. Three genotypes (1b, 2b and 2c) were identified. CONCLUSIONS The frequency of TTV detection depends on the primers used for the PCR. Using the NC primers the virus is detected in the majority of donors, whereas the ORF1 primers strongly underestimate the prevalence of TTV. The frequency of TTV DNA increases with age. Polish TTV isolates are highly polymorphic and are classified as 1b, 2b and 2c.
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Affiliation(s)
- P Grabarczyk
- Institute of Haematology and Blood Transfusion, Warsaw, Poland.
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Kakkola L, Hedman K, Vanrobaeys H, Hedman L, Söderlund-Venermo M. Cloning and sequencing of TT virus genotype 6 and expression of antigenic open reading frame 2 proteins. J Gen Virol 2002; 83:979-990. [PMID: 11961251 DOI: 10.1099/0022-1317-83-5-979] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
The near-full-length genome of a TT virus (TTV) (HEL32), closely related to the previously uncharacterized genotype 6, was cloned and sequenced. The genomic organization of HEL32 was compared to 41 published near-full-length TTV sequences representing 17 genotypes. In the majority of genomes, the open reading frame (ORF) 2 region was divided into two separate ORFs, 2a and 2b. The ORF2a sequence was conserved among all genotypes, while the ORF2b region showed more variability. The two corresponding putative proteins of HEL32 were expressed in prokaryotes and their antigenic potential was studied. IgM and IgG antibodies to the respective ORF2-encoded proteins, fp2a and fp2b, and the presence of TTV DNA were studied in the sera of 89 constitutionally healthy adults. By immunoblot using the small TTV proteins as antigens, strong IgM and IgG reactivities were found in 9 and 10% of subjects, respectively. Follow-up studies for 12-15 years of three subjects showed either a persistent coexistence of IgM and TTV DNA or the appearance of viral DNA regardless of pre-existing antibodies. The low prevalence of IgG could be due to the weak immunogenicity of these probably non-structural proteins or to a genotype-specific antibody response. By nested PCR of the conserved ORF2a region, the prevalence of TTV DNA was 85%. TTV genotype 6 sequences were found by specific PCR in 3 of 35 (8.6%) subjects. The low prevalence of TTV IgG compared to the high TTV DNA prevalence, the coexistence of antibodies and viral DNA and the appearance of TTV DNA regardless of pre-existing antibodies suggest that the B-cell immunity against these minor TTV proteins would not be cross protective.
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Affiliation(s)
- Laura Kakkola
- Department of Virology, Haartman Institute and Helsinki University Central Hospital, POB 21, FIN-00014 University of Helsinki, Finland1
| | - Klaus Hedman
- Department of Virology, Haartman Institute and Helsinki University Central Hospital, POB 21, FIN-00014 University of Helsinki, Finland1
| | - Heidi Vanrobaeys
- Department of Virology, Haartman Institute and Helsinki University Central Hospital, POB 21, FIN-00014 University of Helsinki, Finland1
| | - Lea Hedman
- Department of Virology, Haartman Institute and Helsinki University Central Hospital, POB 21, FIN-00014 University of Helsinki, Finland1
| | - Maria Söderlund-Venermo
- Department of Virology, Haartman Institute and Helsinki University Central Hospital, POB 21, FIN-00014 University of Helsinki, Finland1
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Saback FL, Gomes SA, Niel C. High frequency of mixed TT virus infections in healthy adults and children detected by a simplified heteroduplex mobility assay. J Virol Methods 2002; 101:117-25. [PMID: 11849690 DOI: 10.1016/s0166-0934(01)00425-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Recombinant plasmids carrying 199 base pairs (bp) inserts from the non coding region (nucleotides (nt) 6-204) of the TT virus (TTV) genome were used to standardize an heteroduplex mobility assay able to detect mixed infections of a single individual with several TTV isolates. In this simplified heteroduplex mobility assay, polymerase chain reaction (PCR) products were analyzed directly by polyacrylamide gel electrophoresis, without requirement for post-PCR denaturation and annealing steps of the amplicons. The assay was used to test TTV positive serum samples collected from healthy 1-7 years old children, 11-17 years old adolescents, and 24-39 years old blood donors living in Rio de Janeiro, Brazil, as well as TTV positive samples from Amazonian Indians. The results showed a very high frequency of multiple infection in all groups, with 20/30 (67%), 31/33 (94%), 35/38 (92%), and 34/37 (92%) of the samples collected from children, adolescents, blood donors, and Amazonian Indians, respectively, containing more than one TTV genotype.
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Affiliation(s)
- Felipe L Saback
- Department of Virology, Oswaldo Cruz Institute, Av. Brasil 4365, 21045-900, RJ, Rio de Janeiro, Brazil
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Bez C, Hallett R, Carrozzo M, Lodi G, Gandolfo S, Carrassi A, Scully C, Porter SR. Lack of association between hepatotropic transfusion transmitted virus infection and oral lichen planus in British and Italian populations. Br J Dermatol 2001; 145:990-3. [PMID: 11899155 DOI: 10.1046/j.1365-2133.2001.04518.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND A possible association between oral lichen planus (OLP) and chronic hepatic disease has been found in some populations, although this is probably geographically influenced. In 1997 a new hepatotropic virus, transfusion transmitted virus (TTV), was identified but has not been studied in relation to OLP. OBJECTIVE The present investigation evaluated the genoprevalence of TTV DNA in the sera of British and Italian patients suffering from OLP using two different sets of primers to identify TTV subgenomic DNA. METHODS Study groups comprised 40 adult subjects (21 British, 19 Italian) with OLP. For each country, two control groups, a disease-control group and a healthy-control group, were included. The presence of TTV DNA in the sera of patients and control subjects was assessed using two different polymerase chain reactions (PCR) and DNA sequence analysis. RESULTS Statistical analysis did not reveal evidence of any association between TTV infection and OLP or country of residence. CONCLUSION An association between TTV and OLP is unlikely.
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Affiliation(s)
- C Bez
- Department of Oral Medicine, Eastman Dental Institute for Oral Health Care Sciences, UCL, University of London, UK
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Maggi F, Fornai C, Vatteroni ML, Siciliano G, Menichetti F, Tascini C, Specter S, Pistello M, Bendinelli M. Low prevalence of TT virus in the cerebrospinal fluid of viremic patients with central nervous system disorders. J Med Virol 2001; 65:418-22. [PMID: 11536254 DOI: 10.1002/jmv.2051] [Citation(s) in RCA: 45] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
TT virus (TTV) is a widespread infectious agent of humans identified in 1998. In infected individuals, TTV induces persistent viremia but its life cycle and pathogenic potential are still poorly understood. In the present study, the presence of TTV DNA in 32 consecutive paired serum and cerebrospinal fluid (CSF) samples from patients with neurological (mainly multiple sclerosis) disorders was investigated by means of a sensitive quantitative real-time PCR assay. Of the 24 patients who were found to carry TTV DNA in serum, 3 also had detectable TTV DNA in their CSF. Two TTV positive CSF samples had markers indicative of blood contamination or a disrupted blood-brain barrier and contained considerably lower TTV loads as compared with the corresponding serum samples, thus suggesting that the virus they contained was of plasma origin. These findings indicated that in general TTV does not permeate effectively an intact blood-brain barrier. Furthermore, the CNS does not represent a common site of TTV replication and persistence. However, at least one exception was observed: the third TTV positive CSF sample (obtained from a patient with subacute dementia of unknown origin) showed no markers suggestive of disrupted blood-brain barrier or blood contamination and had a TTV DNA concentration similar to that found in the patient's serum. In addition, the TTV isolates detected in the two body fluids were distinct genetically. The detection of TTV DNA in CSF is of considerable interest but the clinical significance remains unknown.
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Affiliation(s)
- F Maggi
- Retrovirus Center and Virology Section, Department of Biomedicine, University of Pisa, Pisa, Italy
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45
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Maggi F, Fornai C, Zaccaro L, Morrica A, Vatteroni ML, Isola P, Marchi S, Ricchiuti A, Pistello M, Bendinelli M. TT virus (TTV) loads associated with different peripheral blood cell types and evidence for TTV replication in activated mononuclear cells. J Med Virol 2001; 64:190-4. [PMID: 11360252 DOI: 10.1002/jmv.1035] [Citation(s) in RCA: 82] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
TT virus (TTV) loads associated with the peripheral blood cells of seven patients known to carry the virus in plasma were investigated by real-time PCR. Whereas red cells/platelets were uniformly negative, six and four patients yielded positive peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes, respectively, but viral titres were generally low. Fractionation of PBMCs into monocyte- and B, T4, and T8 lymphocyte-enriched subpopulations showed no pattern in the viral loads that might suggest the preferential association of TTV to one or more specific cell types. TTV-negative PBMCs absorbed measurable amounts of virus when incubated with infected plasma at 4 degrees C. Furthermore, cultures of TTV-negative phytohaemagglutinin-stimulated PBMCs exposed in vitro to virus-positive plasma and faecal extracts released considerable levels of infectious TTV into the supernatant fluid and the same was true for TTV-positive stimulated PBMCs. These results indicate that, whereas freshly harvested resting PBMCs seem to produce little, if any TTV, stimulated PBMCs actively replicate the virus.
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Affiliation(s)
- F Maggi
- Virology Section and Retrovirus Centre, Department of Biomedicine, University of Pisa, Via San Zeno 37, I-56127 Pisa, Italy
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46
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Touinssi M, Gallian P, Biagini P, Attoui H, Vialettes B, Berland Y, Tamalet C, Dhiver C, Ravaux I, De Micco P, De Lamballerie X. TT virus infection: prevalence of elevated viraemia and arguments for the immune control of viral load. J Clin Virol 2001; 21:135-41. [PMID: 11378494 DOI: 10.1016/s1386-6532(01)00157-3] [Citation(s) in RCA: 70] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND The most recent polymerase chain reaction (PCR) detection protocols for the TT virus (TTV) permit one to identify the presence of viral DNA in the serum of a majority of healthy individuals, in the absence of any particular risk factor. This is in contrast with previous epidemiological studies that reported a higher prevalence of TTV infection in populations such as haemodialysis patients (HD), haemophiliacs, intravenous drug users or diabetics. OBJECTIVES To show that these discrepant results were due to the different sensitivity (number of viral copies detected) of the detection protocols used in initial and more recent epidemiological studies. STUDY DESIGN AND RESULTS We designed a standardised primary PCR assay that detects only viraemia >5x10(3) to 5x10(4) copies/ml for genotypes 1, 2 and 3, and compared the results of this test with those of a nested PCR assay which is 100-fold more sensitive. Viraemia >5x10(3) to 5x10(4) copies/ml were statistically more frequent in HD patients (54.3%), diabetics (54.7%), and HIV-infected patients with CD4 cells <200/mm(3) (69%) than in blood donors (37%) or HIV-infected patients with CD4 cells >500/mm(3) (33%). CONCLUSIONS These data suggest a possible relationship between the prevalence of elevated viral loads and the level of immunocompetence of the populations studied, and therefore that of an immune control of TTV viraemia. This corroborates previous findings showing that the stimulation of the immune system by an interferon treatment was able to clear TTV viraemia.
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Affiliation(s)
- M Touinssi
- Unité des Virus Emergents, Laboratoire de Virologie Moléculaire, Tropicale et Transfusionnelle, Faculté de Médecine de Marseille, Boulevard Jean Moulin, 13385 Marseille cedex 05, France
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Sugiyama K, Goto K, Ando T, Mizutani F, Terabe K, Yokoyama T. Highly diverse TTV population in infants and their mothers. Virus Res 2001; 73:183-8. [PMID: 11172922 DOI: 10.1016/s0168-1702(00)00242-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Infants born to serum HCV-positive 12 mothers were enrolled in the study. Nucleotide sequences amplified by primers deduced from a noncoding region were compared between mothers and their infants. The rates for detection of serum TTV in 12 mothers and their infants were 10/12 (83%) and 9/12 (75%), respectively. Serum TTV DNA was not detected in any infant at 1 month of age, but was detected for the first time between 1.5 and 8 months after birth. Positivity persisted thereafter throughout the follow-up period. In seven randomly selected mother-infant pairs, intrahost TTV heterogeneity was lower in infants than in mothers. Furthermore, one of seven mother-infant pairs showed a high degree of similarity (98.7-100%) in all clones, while in four infants, all nucleotide sequences differed by >10% from those of their mothers. However, the degree of homology in the two mother-infant pairs was 89-98.7% in family 2 and 88.1-99.4% in family 5. In the present study, with only one exception, it was shown that TTV from infants is not identical to TTV from mothers. The mechanism is discussed briefly in this paper.
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Affiliation(s)
- K Sugiyama
- Department of Pediatrics, Nagoya City University Medical School, Kawasumi-cho, Mizuho-ku, 467-8601, Nagoya, Japan.
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48
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Abstract
Following the development of tests for hepatitis C virus and hepatitis E virus infection, it became clear that there remained cases of hepatitis that were non-A-E. Such cases provided impetus for the search for additional hepatitis viruses and, by using molecular techniques, several candidates were identified. An enteric agent responsible for sporadic non-A and non-E hepatitis was tentatively called hepatitis F virus. However, the lack of any corroborating reports has cast doubt on its status as a true hepatitis virus. Two groups independently reported the isolation of a blood-borne virus, designated as hepatitis G virus (HGV) and GB virus C (GBV-C) by their respective discoverers. They were later shown to be isolates of the same virus. While the virus has a high prevalence in cases of non-A-E hepatitis, it also has a high prevalence in the appropriate control groups and convincing evidence for its replication in the liver is lacking. Another possible hepatitis virus, TT virus, was discovered in the blood of a patient with post-transfusion non-A-E hepatitis. By using PCR primers designed to overcome the high nucleotide sequence divergence, TT virus was found to be ubiquitous with a worldwide distribution. A disease association is thus unlikely. Most recently, a DNA virus designated as SEN-V has been announced as a major cause of non-A-E hepatitis. Based on limited data available to researchers, SEN-V is the most convincing contender for the new hepatitis virus title. However, the lessons learnt from the hepatitis virus pretenders will need to be applied to SEN-V and any future contenders.
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Affiliation(s)
- S Bowden
- Victorian Infectious Diseases Reference Laboratory, North Melbourne, Australia.
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49
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Biagini P, Gallian P, Attoui H, Touinssi M, Cantaloube JF, de Micco P, de Lamballerie X. Genetic analysis of full-length genomes and subgenomic sequences of TT virus-like mini virus human isolates. J Gen Virol 2001; 82:379-383. [PMID: 11161277 DOI: 10.1099/0022-1317-82-2-379] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
The phylogenetic relationship between the complete genomic sequences of ten Japanese and one French isolate of TT virus-like mini virus (TLMV) was investigated. Analysis of the variability of the nucleotide sequences and the detection of signature patterns for overlapping genes suggested that ORFs 1 and 2 are probably functional. However, this was not the case for a putative third ORF, ORF3. Throughout the viral genome, several nucleotide or amino acid motifs that are conserved in circoviruses such as TT virus (TTV) and chicken anaemia virus were identified. Phylogenetic analysis distinguished three main groups of TLMV and allowed the identification of putative recombination breakpoints in the untranslated region. TLMV genomes were detected by PCR in the plasma of 38/50 French blood donors tested and were also identified in peripheral blood mononuclear cells, faeces and saliva. A phylogenetic study of 37 TLMV strains originating from France, Japan and Brazil showed that groupings were not related to geographical origin.
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Affiliation(s)
- Philippe Biagini
- Unité des Virus Emergents, EA 871, Laboratoire de Virologie Moléculaire, Établissement Français du Sang 'Alpes-Méditerranée', 149 Boulevard Baille, 13005 Marseille, France1
| | - Pierre Gallian
- Unité des Virus Emergents, EA 871, Laboratoire de Virologie Moléculaire, Établissement Français du Sang 'Alpes-Méditerranée', 149 Boulevard Baille, 13005 Marseille, France1
| | - Houssam Attoui
- Unité des Virus Emergents, EA 871, Laboratoire de Virologie Moléculaire, Établissement Français du Sang 'Alpes-Méditerranée', 149 Boulevard Baille, 13005 Marseille, France1
| | - Mhammed Touinssi
- Unité des Virus Emergents, EA 871, Laboratoire de Virologie Moléculaire, Établissement Français du Sang 'Alpes-Méditerranée', 149 Boulevard Baille, 13005 Marseille, France1
| | - Jean-François Cantaloube
- Unité des Virus Emergents, EA 871, Laboratoire de Virologie Moléculaire, Établissement Français du Sang 'Alpes-Méditerranée', 149 Boulevard Baille, 13005 Marseille, France1
| | - Philippe de Micco
- Unité des Virus Emergents, EA 871, Laboratoire de Virologie Moléculaire, Tropicale et Transfusionnelle, Faculté de Médecine, 27 Boulevard Jean Moulin, 13005 Marseille, France2
- Unité des Virus Emergents, EA 871, Laboratoire de Virologie Moléculaire, Établissement Français du Sang 'Alpes-Méditerranée', 149 Boulevard Baille, 13005 Marseille, France1
| | - Xavier de Lamballerie
- Unité des Virus Emergents, EA 871, Laboratoire de Virologie Moléculaire, Tropicale et Transfusionnelle, Faculté de Médecine, 27 Boulevard Jean Moulin, 13005 Marseille, France2
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Abstract
The increasing pace of development in molecular biological techniques during the last 10-15 years has had a direct effect on mass testing and diagnostic applications, including blood screening. Nucleic acid amplification techniques (NAT), usually based on the polymerase chain reaction (PCR), have been successfully applied to blood grouping and implemented recently in screening of blood donations for hepatitis C virus (HCV). The majority of microarray technologies involve an amplification step, yet the main benefits of this technology come from simultaneous analysis of thousands of analytes. Microarrays were developed to utilize the huge amount of information provided by genome projects, but they have clear potential in mass screening and diagnostics. The application of microarray technology may revolutionize blood testing, providing for the first time the prospect of an integrated platform for comprehensive donor and donation testing, replacing multiple individual assays. Design features of a blood-testing chip and various technologies with potential application in this field are discussed in this review.
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Affiliation(s)
- J Petrik
- Scottish National Blood Transfusion Service, NAT Reference Lab, LCMV, Royal (Dick) Veterinary College, Summerhall, Edinburgh EH9 10H.
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