|
1
|
Acharya A, Byrareddy SN. Immunological insights into the re-emergence of human metapneumovirus. Curr Opin Immunol 2025; 94:102562. [PMID: 40359650 PMCID: PMC12166946 DOI: 10.1016/j.coi.2025.102562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 04/19/2025] [Accepted: 04/24/2025] [Indexed: 05/15/2025]
Abstract
Human metapneumovirus (hMPV) is a seasonal respiratory virus that typically causes mild, flu-like symptoms. In some cases, it can lead to severe respiratory complications, such as pneumonia, bronchitis, and bronchiolitis, often requiring hospitalization. Recently, a surge in hMPV cases has been reported in China and other countries, raising concerns about a potential pandemic scenario reminiscent of COVID-19. This review explores the genomic structure, replication cycle, genetic diversity, and evolutionary trajectory of hMPV. It also discusses host immune responses and the available animal models to study pathogenesis and to screen for potential vaccines and antivirals. Additionally, we examine the shifting seasonal trends in hMPV circulation, evaluate the low pandemic risk posed by existing hMPV clades, and underscore the need for continued vaccine and antiviral development. Finally, we advocate for strengthened global surveillance, especially in low- and middle-income countries, as a critical strategy to mitigate the risks posed by emerging hMPV clades.
Collapse
Affiliation(s)
- Arpan Acharya
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States
| | - Siddappa N Byrareddy
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States.
| |
Collapse
|
|
2
|
Bhuvaneshwari V, Amsaveni R. Exploring quercetin based nano formulation in combating human Metapneumovirus infections. Int Immunopharmacol 2025; 153:114510. [PMID: 40132458 DOI: 10.1016/j.intimp.2025.114510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2025] [Revised: 02/16/2025] [Accepted: 03/16/2025] [Indexed: 03/27/2025]
Abstract
Human Metapneumovirus (hMPV) is a significant respiratory pathogen, particularly affecting children, the elderly, and immunocompromised individuals. Despite its clinical impact, there are currently no approved vaccines or specific antiviral treatments for hMPV, necessitating the exploration of novel therapeutic strategies. Quercetin, a naturally occurring flavonoid with well-documented antioxidant, anti-inflammatory, and antiviral properties, has shown promising potential in combating hMPV infections. However, its poor bioavailability limits its therapeutic efficacy. Recent advancements in nanotechnology offer a solution through quercetin-based nanoformulations, which enhance its solubility, stability, and bioavailability, thereby improving its antiviral potency. Molecular docking studies have demonstrated strong interactions between quercetin and the hMPV matrix protein, suggesting its role in inhibiting viral replication. Additionally, quercetin modulates oxidative stress and inflammatory responses by suppressing key pathways such as NF-κB and IRF-3, reducing lung damage associated with hMPV infections. In vitro and in vivo studies indicate that quercetin-loaded nanoparticles effectively decrease viral titers and inflammatory markers. Given its natural origin, safety profile, and therapeutic potential, quercetin-based nanoformulations emerge as a promising candidate for hMPV treatment. Further clinical trials are required to validate their efficacy and optimize formulations for potential clinical application.
Collapse
Affiliation(s)
- Veluswamy Bhuvaneshwari
- Department of Biotechnology, PSGR Krishnammal College for Women, Coimbatore 641004, Tamil Nadu, India.
| | - Ramasamy Amsaveni
- Department of Biotechnology, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India
| |
Collapse
|
|
3
|
Georgakopoulou VE. Insights from respiratory virus co-infections. World J Virol 2024; 13:98600. [PMID: 39722753 PMCID: PMC11551690 DOI: 10.5501/wjv.v13.i4.98600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 08/26/2024] [Accepted: 08/28/2024] [Indexed: 10/18/2024] Open
Abstract
Respiratory viral co-infections present significant challenges in clinical settings due to their impact on disease severity and patient outcomes. Current diagnostic methods often miss these co-infections, complicating the epidemiology and management of these cases. Research, primarily conducted in vitro and in vivo, suggests that co-infections can lead to more severe illnesses, increased hospitalization rates, and greater healthcare utilization, especially in high-risk groups such as children, the elderly, and immunocompromised individuals. Common co-infection patterns, risk factors, and their impact on disease dynamics highlight the need for advanced diagnostic techniques and tailored therapeutic strategies. Understanding the virological interactions and immune response modulation during co-infections is crucial for developing effective public health interventions and improving patient outcomes. Future research should focus on the molecular mechanisms of co-infection and the development of specific therapies to mitigate the adverse effects of these complex infections.
Collapse
Affiliation(s)
- Vasiliki E Georgakopoulou
- Department of Pathophysiology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens 11527, Greece
| |
Collapse
|
|
4
|
Shirato K, Suwa R, Nao N, Kawase M, Sugimoto S, Kume Y, Chishiki M, Ono T, Okabe H, Norito S, Sato M, Sakuma H, Suzuki S, Hosoya M, Takeda M, Hashimoto K. Molecular Epidemiology of Human Metapneumovirus in East Japan before and after COVID-19, 2017-2022. Jpn J Infect Dis 2024; 77:137-143. [PMID: 38171847 DOI: 10.7883/yoken.jjid.2023.350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2024]
Abstract
Human metapneumovirus (hMPV) is genetically classified into two major subgroups, A and B, based on attachment glycoprotein (G protein) gene sequences. The A2 subgroup is further separated into three subdivisions, A2a, A2b (A2b1), and A2c (A2b2). Subgroup A2c viruses carrying 180- or 111-nucleotide duplications in the G gene (A2c 180nt-dup or A2c 111nt-dup ) have been reported in Japan and Spain. The coronavirus disease 2019 (COVID-19) pandemic disrupted the epidemiological kinetics of other respiratory viruses, including hMPV. In this study, we analyzed the sequences of hMPV isolates in Tokyo and Fukushima obtained from 2017 to 2022, i.e., before and after the COVID-19 pandemic. Subgroup A hMPV strains were detected from 2017 to 2019, and most cases were A2c 111nt-dup, suggesting ongoing transmission of this clade, consistent with global transmission dynamics. Subgroup B viruses, but not subgroup A viruses, were detected in 2022 after the COVID-19 peak. Phylogenetic analysis showed that the subgroup B viruses were closely related to strains detected in Yokohama from 2013 to 2016, and strains detected in Fukushima in 2019, suggesting the reappearance of local endemic viruses in East Japan.
Collapse
Affiliation(s)
- Kazuya Shirato
- Department of Virology III, National Institute of Infectious Diseases, Japan
| | - Reiko Suwa
- Department of Virology III, National Institute of Infectious Diseases, Japan
| | - Naganori Nao
- Department of Virology III, National Institute of Infectious Diseases, Japan
- One Health Research Center, International Institute for Zoonosis Control, Hokkaido University, Japan
- Division of International Research Promotion, International Institute for Zoonosis Control, Hokkaido University, Japan
| | - Miyuki Kawase
- Department of Virology III, National Institute of Infectious Diseases, Japan
| | - Satoko Sugimoto
- Department of Virology III, National Institute of Infectious Diseases, Japan
- Management Department of Biosafety, Laboratory Animals, and Pathogen Bank, National Institute of Infectious Diseases, Japan
| | - Yohei Kume
- Department of Pediatrics, School of Medicine, Fukushima Medical University, Japan
| | - Mina Chishiki
- Department of Pediatrics, School of Medicine, Fukushima Medical University, Japan
| | - Takashi Ono
- Department of Pediatrics, School of Medicine, Fukushima Medical University, Japan
| | - Hisao Okabe
- Department of Pediatrics, School of Medicine, Fukushima Medical University, Japan
| | - Sakurako Norito
- Department of Pediatrics, School of Medicine, Fukushima Medical University, Japan
| | - Masatoki Sato
- Department of Pediatrics, School of Medicine, Fukushima Medical University, Japan
| | | | | | - Mitsuaki Hosoya
- Department of Pediatrics, School of Medicine, Fukushima Medical University, Japan
| | - Makoto Takeda
- Department of Virology III, National Institute of Infectious Diseases, Japan
- Department of Microbiology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Japan
| | - Koichi Hashimoto
- Department of Pediatrics, School of Medicine, Fukushima Medical University, Japan
| |
Collapse
|
|
5
|
Ma S, Zhu F, Xu Y, Wen H, Rao M, Zhang P, Peng W, Cui Y, Yang H, Tan C, Chen J, Pan P. Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus. Hum Vaccin Immunother 2023; 19:2293300. [PMID: 38172569 PMCID: PMC10824151 DOI: 10.1080/21645515.2023.2293300] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 12/06/2023] [Indexed: 01/05/2024] Open
Abstract
Human metapneumovirus (HMPV) is one of the main pathogens causing severe respiratory infections in children, as a common cause of immunodeficiency-related deaths in children and elderly individuals, the prevalence of HMPV has been showing an increasing trend during the last years. However, no vaccines or effective treatment plans are available currently. In this present, based on candidate proteins highly associated with viral virulence and has promising protective potential, we screened for immunodominant cytotoxic T cells, helper T cells, and Linear B-cell epitopes from the most promising candidate Fusion protein, together with G, SH, M, and M2. All epitopes were predicted to have strong antigenicity by Vaxijen and pose no potential toxicity, allergenicity, or hormonology to human proteins by Toxinpred, Allerpred, and Blast analysis, meanwhile, high conservancy is demanded to cover different subtypes. adjuvants β-defensin II and Pam2Cys was attached with EAAAK linkers to improve vaccine's efficiency. Then, calculation of physicochemical properties proved the protein vaccine as a product can stably exist in the human body. Besides, we assessed the docking between the vaccine and immune receptors to evaluate its ability to stimulate immune responses, and the dynamic simulation further confirmed that the vaccine can tightly bind with immune receptors, which approved that the construction has the potential to induce strong humoral and cellular immune response. Finally, the vaccine was constructed into a multi-epitope mRNA vaccine, the immune simulations suggest that this is a vaccine candidate for controlling HMPV infection.
Collapse
Affiliation(s)
- Shiyang Ma
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Fei Zhu
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Yizhong Xu
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Haicheng Wen
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Mingjun Rao
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Peipei Zhang
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Wenzhong Peng
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Yanhui Cui
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Hang Yang
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Caixia Tan
- Department of Infection Control Center of Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Jie Chen
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Pinhua Pan
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| |
Collapse
|
|
6
|
Velayutham TS, Ivanciuc T, Garofalo RP, Casola A. Role of human metapneumovirus glycoprotein G in modulation of immune responses. Front Immunol 2022; 13:962925. [PMID: 35958551 PMCID: PMC9357950 DOI: 10.3389/fimmu.2022.962925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 07/01/2022] [Indexed: 11/13/2022] Open
Abstract
Human metapneumovirus (hMPV) is an important pathogen responsible for acute respiratory tract infections in children, the elderly, and immunocompromised patients, with no effective treatment or vaccine currently available. Knowledge of virus- and host-specific mechanisms contributing to the pathogenesis of hMPV infection is still limited. Studies have shown that hMPV surface glycoprotein G is an important virulence factor, by inhibiting innate immune signaling in airway epithelial cells and immune cells. In this study, we investigated the role of G protein in modulating innate and adaptive immune responses in mice infected with a recombinant virus with deletion of G protein (rhMPV-ΔG). Results show that rhMPV-ΔG was strongly attenuated, as it did not induce significant clinical disease, airway obstruction and airway hyperresponsiveness (AHR), compared to infection with a control strain (rhMPV-WT). By analysis of cells in bronchoalveolar fluid and lung tissue, as well as cytokine production, we found that G protein mediates aspects of both innate and adaptive immune responses, including neutrophils, dendritic cells, natural killer cells and B cells. Lung T cells recruited in response to rhMPV-ΔG had a significantly higher activated phenotype compared to those present after rhMPV-WT infection. Despite highly attenuation characterized by low levels of replication in the lung, rhMPV-ΔG was able to induce neutralizing antibodies and to protect mice from a secondary hMPV challenge. However, challenged mice that had received rhMPV-ΔG as primary infection showed some signs of lung disease at the earliest time points, which were less evident in mice that had received the rhMPV-WT strain as primary infection. These results demonstrate some of the mechanisms by which G protein could contribute to airway disease and modulate immune response to hMPV infection.
Collapse
Affiliation(s)
| | - Teodora Ivanciuc
- Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, United States
| | - Roberto P. Garofalo
- Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, United States
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States
- Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, United States
- *Correspondence: Antonella Casola, ; Roberto P. Garofalo,
| | - Antonella Casola
- Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, United States
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States
- Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, United States
- *Correspondence: Antonella Casola, ; Roberto P. Garofalo,
| |
Collapse
|
|
7
|
Nunes DBSM, Vieira C, Sá JM, Araújo GC, Caruso IP, Souza FP. M2-2 gene as a new alternative molecular marker for phylogenetic, phylodynamic, and evolutionary studies of hRSV. Virus Res 2022; 318:198850. [PMID: 35750131 DOI: 10.1016/j.virusres.2022.198850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 06/11/2022] [Accepted: 06/17/2022] [Indexed: 10/18/2022]
Abstract
The human Respiratory Syncytial Virus (hRSV) is the main causative agent of acute respiratory infections (ARI), such as pneumonia and bronchiolitis. One of the factors that lead to success in viral replication is the interaction of the M2-2 protein with the ribosomal complex. This interaction is responsible for the phase change of viral activity, acting as an inhibitor or inducer of viral replication, according to the concentration of mRNA. Based on the importance of M2-2 gene and protein have to viral physiology, we performed here evaluations of genetic diversity, phylogenetic reconstructions, phylodynamics, and selection test. Our results suggested an alternative way of classifying this virus in clades A and B, based on a new phylogenetic marker, the M2-2 gene. Therefore, our study is the first one to investigate the dynamics of the evolutionary diversification process of hRSV from the perspective of the M2-2 viral gene. In our study was also identified that the M2-2 gene is under the effect of purifying selection originated by population genetic bottlenecks. Therefore, the M2-2 gene demonstrated an interesting potential to be applied in evolutionary studies involving hRSV, recovering phylogenetic signals and traits of natural selection under the evolution of this virus.
Collapse
Affiliation(s)
- Denis Bruno S M Nunes
- Institute of Biological and Health Sciences, Federal University of Alagoas (UFAL), Campus A.C. Simões, AL, Brazil
| | - Camila Vieira
- Department of Basic Sciences, Faculty of Animal Science and Food Engineering, University of São Paulo (USP), Pirassununga, SP, Brazil
| | - Jéssica M Sá
- Multiuser Biomolecular Innovation Laboratory, Department of Physics Letters and Exact Sciences, Institute of Biosciences, São Paulo State University "Júlio de Mesquita Filho" (UNESP), São José do Rio Preto, SP, Brazil
| | - Gabriela C Araújo
- Multiuser Biomolecular Innovation Laboratory, Department of Physics Letters and Exact Sciences, Institute of Biosciences, São Paulo State University "Júlio de Mesquita Filho" (UNESP), São José do Rio Preto, SP, Brazil
| | - Icaro P Caruso
- Multiuser Biomolecular Innovation Laboratory, Department of Physics Letters and Exact Sciences, Institute of Biosciences, São Paulo State University "Júlio de Mesquita Filho" (UNESP), São José do Rio Preto, SP, Brazil; Institute of Medical Biochemistry Leopoldo de Meis and National Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil.
| | - Fátima P Souza
- Multiuser Biomolecular Innovation Laboratory, Department of Physics Letters and Exact Sciences, Institute of Biosciences, São Paulo State University "Júlio de Mesquita Filho" (UNESP), São José do Rio Preto, SP, Brazil.
| |
Collapse
|
|
8
|
Stein M, Cohen H, Nemet I, Atari N, Kliker L, Fratty IS, Bucris E, Geva M, Mendelson E, Zuckerman N, Mandelboim M. Human metapneumovirus prevalence during 2019-2021 in Israel is influenced by the COVID-19 pandemic. Int J Infect Dis 2022; 120:205-209. [PMID: 35472530 DOI: 10.1016/j.ijid.2022.04.037] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 04/03/2022] [Accepted: 04/20/2022] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVES To compare infection rates and circulating subtypes of human metapneumovirus (hMPV) before (2019-2020) and after the emergence of coronavirus disease 2019 (COVID-19) (2021) in Israel. METHODS In total, 12,718 respiratory samples were collected from hospitalized patients of all ages during the years 2019 to 2021 at the Sheba Medical Center in Israel and subjected to reverse transcription-polymerase chain reaction analysis. In addition, whole-genome sequencing was performed to characterize the subtypes of hMPV circulating in Israel between 2019 and 2021. RESULTS A total of 481 samples were found positive for hMPV. Before the emergence of COVID-19, hMPV peaked in winter months and declined thereafter. In sharp contrast, during the COVID-19 pandemic, we observed a delayed peak in hMPV infection cases and higher infection of young children. Viral sequencing showed a shift in the most prevalent circulating hMPV strain from A2b to B1 during the years 2019, 2020, and 2021. CONCLUSION Compared with the years before the COVID-19 pandemic, in 2021, hMPV mostly affected young children, and the most prevalent circulating subtype shifted from A2b in 2019 to B1.
Collapse
Affiliation(s)
- Michal Stein
- Pediatric Infectious Disease Unit, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel
| | - Hodaya Cohen
- Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel
| | - Ital Nemet
- Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel
| | - Nofar Atari
- Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel
| | - Limor Kliker
- Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel
| | - Ilana S Fratty
- Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel
| | - Efrat Bucris
- Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel
| | - Miranda Geva
- Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel
| | - Ella Mendelson
- Sackler Faculty of Medicine, Tel-Aviv University, Israel; Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel
| | - Neta Zuckerman
- Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel
| | - Michal Mandelboim
- Sackler Faculty of Medicine, Tel-Aviv University, Israel; Central Virology Laboratory, Public Health Services, Ministry of Health and Sheba Medical Center, Tel-Hashomer, Israel.
| |
Collapse
|
|
9
|
Saito M, Tsukagoshi H, Sada M, Sunagawa S, Shirai T, Okayama K, Sugai T, Tsugawa T, Hayashi Y, Ryo A, Takeda M, Kawashima H, Saruki N, Kimura H. Detailed Evolutionary Analyses of the F Gene in the Respiratory Syncytial Virus Subgroup A. Viruses 2021; 13:v13122525. [PMID: 34960794 PMCID: PMC8706373 DOI: 10.3390/v13122525] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/06/2021] [Accepted: 12/13/2021] [Indexed: 11/20/2022] Open
Abstract
We performed evolution, phylodynamics, and reinfection-related antigenicity analyses of respiratory syncytial virus subgroup A (RSV-A) fusion (F) gene in globally collected strains (1465 strains) using authentic bioinformatics methods. The time-scaled evolutionary tree using the Bayesian Markov chain Monte Carlo method estimated that a common ancestor of the RSV-A, RSV-B, and bovine-RSV diverged at around 450 years ago, and RSV-A and RSV-B diverged around 250 years ago. Finally, the RSV-A F gene formed eight genotypes (GA1-GA7 and NA1) over the last 80 years. Phylodynamics of RSV-A F gene, including all genotype strains, increased twice in the 1990s and 2010s, while patterns of each RSV-A genotype were different. Phylogenetic distance analysis suggested that the genetic distances of the strains were relatively short (less than 0.05). No positive selection sites were estimated, while many negative selection sites were found. Moreover, the F protein 3D structure mapping and conformational epitope analysis implied that the conformational epitopes did not correspond to the neutralizing antibody binding sites of the F protein. These results suggested that the RSV-A F gene is relatively conserved, and mismatches between conformational epitopes and neutralizing antibody binding sites of the F protein are responsible for the virus reinfection.
Collapse
Affiliation(s)
- Mariko Saito
- Gunma Prefectural Institute of Public Health and Environmental Sciences, Maebashi-shi 371-0052, Japan; (M.S.); (H.T.); (N.S.)
| | - Hiroyuki Tsukagoshi
- Gunma Prefectural Institute of Public Health and Environmental Sciences, Maebashi-shi 371-0052, Japan; (M.S.); (H.T.); (N.S.)
| | - Mitsuru Sada
- Department of Health Science, Gunma Paz University Graduate School, Takasaki-shi 370-0006, Japan; (M.S.); (S.S.); (K.O.); (Y.H.)
| | - Soyoka Sunagawa
- Department of Health Science, Gunma Paz University Graduate School, Takasaki-shi 370-0006, Japan; (M.S.); (S.S.); (K.O.); (Y.H.)
| | - Tatsuya Shirai
- Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka-shi 181-8611, Japan;
| | - Kaori Okayama
- Department of Health Science, Gunma Paz University Graduate School, Takasaki-shi 370-0006, Japan; (M.S.); (S.S.); (K.O.); (Y.H.)
| | - Toshiyuki Sugai
- Division of Nursing Science, Hiroshima University, Hiroshima-shi 734-8551, Japan;
| | - Takeshi Tsugawa
- Department of Pediatrics, Sapporo Medical University School of Medicine, Sapporo-shi 060-8543, Japan;
| | - Yuriko Hayashi
- Department of Health Science, Gunma Paz University Graduate School, Takasaki-shi 370-0006, Japan; (M.S.); (S.S.); (K.O.); (Y.H.)
| | - Akihide Ryo
- Department of Microbiology, Yokohama City University School of Medicine, Yokohama-shi 236-0004, Japan;
| | - Makoto Takeda
- Department of Virology, National Institute of Infectious Diseases, Musashimurayama-shi 208-0011, Japan;
| | - Hisashi Kawashima
- Department of Pediatrics, Tokyo Medical University, Shinjuku-ku 160-0023, Japan;
| | - Nobuhiro Saruki
- Gunma Prefectural Institute of Public Health and Environmental Sciences, Maebashi-shi 371-0052, Japan; (M.S.); (H.T.); (N.S.)
| | - Hirokazu Kimura
- Department of Health Science, Gunma Paz University Graduate School, Takasaki-shi 370-0006, Japan; (M.S.); (S.S.); (K.O.); (Y.H.)
- Correspondence: ; Tel.: +81-27-388-0336
| |
Collapse
|
|
10
|
Kamau E, Otieno JR, Lewa CS, Mwema A, Murunga N, Nokes DJ, Agoti CN. Evolution of respiratory syncytial virus genotype BA in Kilifi, Kenya, 15 years on. Sci Rep 2020; 10:21176. [PMID: 33273687 PMCID: PMC7712891 DOI: 10.1038/s41598-020-78234-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 11/20/2020] [Indexed: 01/12/2023] Open
Abstract
Respiratory syncytial virus (RSV) is recognised as a leading cause of severe acute respiratory disease and deaths among infants and vulnerable adults. Clinical RSV isolates can be divided into several known genotypes. RSV genotype BA, characterised by a 60-nucleotide duplication in the G glycoprotein gene, emerged in 1999 and quickly disseminated globally replacing other RSV group B genotypes. Continual molecular epidemiology is critical to understand the evolutionary processes maintaining the success of the BA viruses. We analysed 735 G gene sequences from samples collected from paediatric patients in Kilifi, Kenya, between 2003 and 2017. The virus population comprised of several genetically distinct variants (n = 56) co-circulating within and between epidemics. In addition, there was consistent seasonal fluctuations in relative genetic diversity. Amino acid changes increasingly accumulated over the surveillance period including two residues (N178S and Q180R) that mapped to monoclonal antibody 2D10 epitopes, as well as addition of putative N-glycosylation sequons. Further, switching and toggling of amino acids within and between epidemics was observed. On a global phylogeny, the BA viruses from different countries form geographically isolated clusters suggesting substantial localized variants. This study offers insights into longitudinal population dynamics of a globally endemic RSV genotype within a discrete location.
Collapse
Affiliation(s)
- Everlyn Kamau
- Epidemiology and Demography Department, Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme, Kilifi, Kenya.
- Nuffield Department of Medicine, University of Oxford, Oxford, UK.
| | - James R Otieno
- Epidemiology and Demography Department, Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme, Kilifi, Kenya
- Fogarty International Center, NIH, Bethesda, MD, USA
| | - Clement S Lewa
- Epidemiology and Demography Department, Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme, Kilifi, Kenya
| | - Anthony Mwema
- Epidemiology and Demography Department, Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme, Kilifi, Kenya
| | - Nickson Murunga
- Epidemiology and Demography Department, Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme, Kilifi, Kenya
| | - D James Nokes
- Epidemiology and Demography Department, Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme, Kilifi, Kenya
- School of Life Sciences and Zeeman Institute (SBIDER), University of Warwick, Coventry, UK
| | - Charles N Agoti
- Epidemiology and Demography Department, Kenya Medical Research Institute (KEMRI) - Wellcome Trust Research Programme, Kilifi, Kenya
- School of Health and Human Sciences, Pwani University, Kilifi, Kenya
| |
Collapse
|
|
11
|
Babaei A, Malekshahi SS, Pirbonyeh N, Sarvari J, Moattari A. Phylogenetic analysis and circulation pattern of human metapneumovirus strains in children with acute respiratory infection in Iran, 2014–2015. Future Virol 2020. [DOI: 10.2217/fvl-2020-0013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aim: The aim of the present study was to investigate the prevalence and genetic variation of the human metapneumovirus (HMPV) G gene in children less than 8 years old with acute respiratory tract infections in Iran during 2014–2015. Materials & methods: To this end, 110 nasal swabs were tested for HMPV F gene. All positive samples were tested for the full length of HMPV G gene, then sequenced and analyzed for phylogenetic grouping. Results: Six (5.45%) out of 110 samples were positive for HMPV gene. Our HMPV sequences clustered into two main clusters: A2b (five isolates) and B1 (one isolate). The dN/dS ratio showed the presence of negative selective pressure. Conclusion: A2b was the predominant genotype during the study period in southwest of Iran.
Collapse
Affiliation(s)
- Abouzar Babaei
- Department of Bacteriology & Virology, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Neda Pirbonyeh
- Department of Bacteriology & Virology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Jamal Sarvari
- Department of Bacteriology & Virology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Afagh Moattari
- Department of Bacteriology & Virology, Shiraz University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
12
|
Zhou Z, Zhang P, Cui Y, Zhang Y, Qin X, Li R, Liu P, Dou Y, Wang L, Zhao Y. Experiments Investigating the Competitive Growth Advantage of Two Different Genotypes of Human Metapneumovirus: Implications for the Alternation of Genotype Prevalence. Sci Rep 2020; 10:2852. [PMID: 32071381 PMCID: PMC7029021 DOI: 10.1038/s41598-020-59150-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Accepted: 01/23/2020] [Indexed: 12/03/2022] Open
Abstract
Human metapneumovirus (hMPV) is an important pathogen that causes upper and lower respiratory tract infections in children worldwide. hMPV has two major genotypes, hMPV-A and hMPV-B. Epidemiological studies have shown that the two hMPV genotypes alternate in predominance worldwide in recent years. Co-circulation of the two genotypes of hMPV was usually observed and there is no study about the interaction between them, such as competitive replication, which maybe the possible mechanisms for alternating prevalence of subtypes. Our present study have used two different genotypes of hMPV (genotype A: NL/1/00; B: NL/1/99) in different proportions in animal model (BALB/c mice) and cell model (Vero-E6) separately. The result showed that the competitive growth does exist in BALB/c mice, genotype B had a strong competitive advantage. However, genotype B did not cause more severe disease than non-predominant (genotype A) or mixed strains in the study, which were evaluated by the body weight, airway hyperresponsiveness and lung pathology of mouse. In cell model, competitive growth and the two genotypes alternately prevalence were observed. In summary, we confirmed that there was a competitive replication between hMPV genotype A and B, and no difference in disease severity caused by the two subtypes. This study shows a new insight to understand the alternation of hMPV genotype prevalence through genotype competition and provide experimental evidence for disease control and vaccine design.
Collapse
Affiliation(s)
- Zhen Zhou
- Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China
| | - Pan Zhang
- Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China
| | - Yuxia Cui
- Department of Pediatrics, Guizhou Provincial People's Hospital, Guizhou, 550002, China
| | - Yongbo Zhang
- Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China
| | - Xian Qin
- Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China
| | - Rongpei Li
- Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China
| | - Ping Liu
- Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China
| | - Ying Dou
- Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China
| | - Lijia Wang
- Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China
- Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China
| | - Yao Zhao
- Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation base of Child development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, P.R. China.
- Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, 400014, China.
| |
Collapse
|
|
13
|
Malekshahi SS, Razaghipour S, Samieipoor Y, Hashemi FB, Manesh AAR, Izadi A, Faghihloo E, Ghavami N, Mokhtari-Azad T, Salimi V. Molecular characterization of the glycoprotein and fusion protein in human respiratory syncytial virus subgroup A: Emergence of ON-1 genotype in Iran. INFECTION GENETICS AND EVOLUTION 2019; 71:166-178. [PMID: 30946992 DOI: 10.1016/j.meegid.2019.03.026] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 03/05/2019] [Accepted: 03/29/2019] [Indexed: 12/20/2022]
Abstract
HRSV is a principle cause of infant hospitalization, childhood wheezing and a common pathogen in the elderly. Limited information exists regarding HRSV genotypes in Iran. In order to better understand HRSV strain diversity, we performed an in-depth evaluation of the genetic variability of the HRSV F protein detected in children under two years of age that, presented with acute respiratory symptoms during 2015-2016 in Tehran. A total of 180 nasopharyngeal swabs were evaluated. The HRSV positive samples were genotyped for G and F gene sequences using RT-PCR and sequencing methods. Phylogenetic analysis was performed using the neighbor-joining and maximum likelihood methods. Genetic and antigenic characteristics of the F gene, nucleotide and amino acids in significant positions and immune system binding regions, as well as the p-distance, positive/negative selection site, linear epitopes and glycosylation sites were investigated in all selected sequences. Among the 83 HRSV positive samples, the Fifty-five cases were successfully sequenced. All of them were classified as subgroup A and belonged to the ON-1 genotype, which possessed 72-nt duplication in the G gene. This study is the first report on the emergence of ON-1 in Iran. ON-1 Iranian sequences clustered in three lineages according to virus fusion (F) gene variations. F gene sequence analysis showed that all genetic changes in the isolates from Iran were base substitutions and no deletion/insertions were identified. The low dN/dS ratio and lack of positively selected sites showed that the fusion genes found in the strains from Iran are not under host selective pressure. Continuing and long-term molecular epidemiological surveys for early detection of circulating and newly emerging genotypes are necessary to gain a better understanding of their epidemic potential.
Collapse
Affiliation(s)
| | - Shaghayegh Razaghipour
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Yazdan Samieipoor
- Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Farhad B Hashemi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Anahita Izadi
- Bahrami Children Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Ebrahim Faghihloo
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nastaran Ghavami
- Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Talat Mokhtari-Azad
- Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahid Salimi
- Virology Department, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
14
|
Divarathne MVM, Ahamed RR, Noordeen F. The Impact of RSV-Associated Respiratory Disease on Children in Asia. J PEDIAT INF DIS-GER 2019; 14:79-88. [PMID: 32300274 PMCID: PMC7117084 DOI: 10.1055/s-0038-1637752] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 02/13/2018] [Indexed: 12/12/2022]
Abstract
Acute respiratory tract infections (ARTIs) are leading contributors to the global infectious disease burden, which is estimated to be 112,900,000 disability adjusted life years. Viruses contribute to the etiology of ARTIs in a big way compared with other microorganisms. Since the discovery of respiratory syncytial virus (RSV) 61 years ago, the virus has been recognized as a major cause of ARTI and hospitalization in children. The morbidity and mortality attributable to RSV infection appear to be higher in infants < 3 months and in those with known risk factors such as prematurity, chronic lung, and congenital heart diseases. Crowded living conditions, exposure to tobacco smoke, and industrial or other types of air pollution also increase the risk of RSV-associated ARTI. Many epidemiological studies have been conducted in developed countries to understand the seasonal patterns and risk factors associated with RSV infections. Dearth of information on RSV-associated morbidity and mortality in Asian and developing countries indicates the need for regional reviews to evaluate RSV-associated disease burden in these countries. Epidemiological studies including surveillance is the key to track the disease burden including risk factors, seasonality, morbidity, and mortality associated with RSV infection in these countries. These data will contribute to improve the clinical diagnosis and plan preventive strategies in resource-limited developing countries.
Collapse
Affiliation(s)
| | - Rukshan Rafeek Ahamed
- Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| | - Faseeha Noordeen
- Department of Microbiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka
| |
Collapse
|
|
15
|
Song J, Wang H, Ng TI, Cui A, Zhu S, Huang Y, Sun L, Yang Z, Yu D, Yu P, Zhang H, Zhang Y, Xu W. Sequence Analysis of the Fusion Protein Gene of Human Respiratory Syncytial Virus Circulating in China from 2003 to 2014. Sci Rep 2018; 8:17618. [PMID: 30514963 PMCID: PMC6279739 DOI: 10.1038/s41598-018-35894-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Accepted: 11/09/2018] [Indexed: 11/09/2022] Open
Abstract
The human respiratory syncytial virus (HRSV) fusion (F) protein is important for HRSV infection, but few studies have examined the genetic diversity of the F gene from Chinese samples. In this study, a total of 330 HRSV F sequences collected from different regions of China between 2003 and 2014 were analyzed to understand their genetic characteristics. In addition, these sequences were compared with 1150 HRSV F sequences in Genbank from 18 other countries. In phylogenetic analysis, Chinese HRSV F sequences sorted into a number of clusters containing sequences from China as well as other countries. F sequences from different genotypes (as determined based on the G gene sequences) within a HRSV subgroup could be found in the same clusters in phylogenetic trees generated based on F gene sequences. Amino acid analysis showed that HRSV F sequences from China and other countries were highly conserved. Of interest, F protein sequences from all Chinese samples were completely conserved at the palivizumab binding site, thus predicting the susceptibility of these strains to this neutralizing antibody. In conclusion, HRSV F sequences from China between 2003 and 2014, similar to those from other countries, were highly conserved.
Collapse
Affiliation(s)
- Jinhua Song
- WHO WPRO Regional Reference Measles/Rubella Laboratory and Key Laboratory of Medical Virology, National Health Commission of the People's Republic of China, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing, People's Republic of China
| | - Huiling Wang
- WHO WPRO Regional Reference Measles/Rubella Laboratory and Key Laboratory of Medical Virology, National Health Commission of the People's Republic of China, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing, People's Republic of China
| | | | - Aili Cui
- WHO WPRO Regional Reference Measles/Rubella Laboratory and Key Laboratory of Medical Virology, National Health Commission of the People's Republic of China, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing, People's Republic of China
| | - Shuangli Zhu
- WHO WPRO Regional Reference Measles/Rubella Laboratory and Key Laboratory of Medical Virology, National Health Commission of the People's Republic of China, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing, People's Republic of China
| | - Yanzhi Huang
- Jilin Children's Medical Center, Children's Hospital of Changchun, Changchun, People's Republic of China
| | - Liwei Sun
- Jilin Children's Medical Center, Children's Hospital of Changchun, Changchun, People's Republic of China
| | - Zifeng Yang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China
| | - Deshan Yu
- Gansu Provincial Centers for Disease Control and Prevention, Lanzhou, People's Republic of China
| | - Pengbo Yu
- Shaanxi Provincial Centers for Disease Control and Prevention, Xian, People's Republic of China
| | - Hong Zhang
- Hunan Provincial Centers for Disease Control and Prevention, Changsha, People's Republic of China
| | - Yan Zhang
- WHO WPRO Regional Reference Measles/Rubella Laboratory and Key Laboratory of Medical Virology, National Health Commission of the People's Republic of China, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing, People's Republic of China.
| | - Wenbo Xu
- WHO WPRO Regional Reference Measles/Rubella Laboratory and Key Laboratory of Medical Virology, National Health Commission of the People's Republic of China, National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, Beijing, People's Republic of China.
| |
Collapse
|
|
16
|
Diaz-Dinamarca DA, Ibañez FJ, Soto DA, Soto JA, Cespedes PF, Muena NA, Garate DS, Kalergis AM, Vasquez AE. Immunization with a Mixture of Nucleoprotein from Human Metapneumovirus and AbISCO-100 Adjuvant Reduces Viral Infection in Mice Model. Viral Immunol 2018; 31:306-314. [PMID: 29373084 DOI: 10.1089/vim.2017.0159] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
The human metapneumovirus (hMPV) is the second leading cause globally of acute infection of the respiratory tract in children, infecting the upper and lower airways. The hMPV may induce an inappropriate Th2-type immune response, which causes severe pulmonary inflammation, leading to the obstruction of airways. Despite its severe epidemiological relevance, no vaccines are currently available for the prevention of hMPV-induced illness. In this investigation, we demonstrated that immunization of mice with the recombinant hMPV nucleoprotein (hMPV-N) mixed with the AbISCO-100 adjuvant reduced viral replication in lungs following challenge with the virus. We found that immunized mice had reduced weight loss, decreased granulocytes in the lung, an increased level of specific nucleoprotein antibodies of IgG1 and IgG2a-isotypes, and a local profile of Th1/Th17-type cytokines. Our results suggest that immunization with the hMPV-N and the AbISCO-100 adjuvant induces a reduction of viral infection and could be considered for the development of an hMPV vaccine.
Collapse
Affiliation(s)
- Diego A Diaz-Dinamarca
- 1 Sección de Biotecnología, Departamento de Salud Ambiental, Instituto de Salud Pública de Chile , Santiago, Chile .,2 Facultad de Ciencias Biológicas, Departamento de Genética Molecular y Microbiología, Millenium Institute on Immunology and Immunotherapy , Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Francisco J Ibañez
- 1 Sección de Biotecnología, Departamento de Salud Ambiental, Instituto de Salud Pública de Chile , Santiago, Chile .,2 Facultad de Ciencias Biológicas, Departamento de Genética Molecular y Microbiología, Millenium Institute on Immunology and Immunotherapy , Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Daniel A Soto
- 1 Sección de Biotecnología, Departamento de Salud Ambiental, Instituto de Salud Pública de Chile , Santiago, Chile
| | - Jorge A Soto
- 1 Sección de Biotecnología, Departamento de Salud Ambiental, Instituto de Salud Pública de Chile , Santiago, Chile .,2 Facultad de Ciencias Biológicas, Departamento de Genética Molecular y Microbiología, Millenium Institute on Immunology and Immunotherapy , Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Pablo F Cespedes
- 2 Facultad de Ciencias Biológicas, Departamento de Genética Molecular y Microbiología, Millenium Institute on Immunology and Immunotherapy , Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Nicolás A Muena
- 1 Sección de Biotecnología, Departamento de Salud Ambiental, Instituto de Salud Pública de Chile , Santiago, Chile
| | - Diego S Garate
- 1 Sección de Biotecnología, Departamento de Salud Ambiental, Instituto de Salud Pública de Chile , Santiago, Chile
| | - Alexis M Kalergis
- 2 Facultad de Ciencias Biológicas, Departamento de Genética Molecular y Microbiología, Millenium Institute on Immunology and Immunotherapy , Pontificia Universidad Católica de Chile, Santiago, Chile .,3 Facultad de Medicina, Departamento de Endocrinología, Pontificia Universidad Católica de Chile , Santiago, Chile
| | - Abel E Vasquez
- 1 Sección de Biotecnología, Departamento de Salud Ambiental, Instituto de Salud Pública de Chile , Santiago, Chile .,4 Universidad San Sebastián , Facultad de Ciencia, Escuela de Bioquímica, Providencia, Santiago, Chile
| |
Collapse
|
|
17
|
Kimura H, Nagasawa K, Kimura R, Tsukagoshi H, Matsushima Y, Fujita K, Hirano E, Ishiwada N, Misaki T, Oishi K, Kuroda M, Ryo A. Molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B. INFECTION GENETICS AND EVOLUTION 2017; 52:1-9. [PMID: 28414106 DOI: 10.1016/j.meegid.2017.04.015] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 04/09/2017] [Accepted: 04/12/2017] [Indexed: 11/19/2022]
Abstract
In this study, we examined the molecular evolution of the fusion protein (F) gene in human respiratory syncytial virus subgroup B (HRSV-B). First, we performed time-scale evolution analyses using the Bayesian Markov chain Monte Carlo (MCMC) method. Next, we performed genetic distance, linear B-cell epitope prediction, N-glycosylation, positive/negative selection site, and Bayesian skyline plot analyses. We also constructed a structural model of the F protein and mapped the amino acid substitutions and the predicted B-cell epitopes. The MCMC-constructed phylogenetic tree indicated that the HRSV F gene diverged from the bovine respiratory syncytial virus gene approximately 580years ago and had a relatively low evolutionary rate (7.14×10-4substitutions/site/year). Furthermore, a common ancestor of HRSV-A and -B diverged approximately 290years ago, while HRSV-B diverged into three clusters for approximately 60years. The genetic similarity of the present strains was very high. Although a maximum of 11 amino acid substitutions were observed in the structural model of the F protein, only one strain possessed an amino acid substitution located within the palivizumab epitope. Four epitopes were predicted, although these did not correspond to the neutralization sites of the F protein including the palivizumab epitope. In addition, five N-glycosylation sites of the present HRSV-B strains were inferred. No positive selection sites were identified; however, many sites were found to be under negative selection. The effective population size of the gene has remained almost constant. On the basis of these results, it can be concluded that the HRSV-B F gene is highly conserved, as is the F protein of HRSV-A. Moreover, our prediction of B-cell epitopes does not show that the palivizumab reaction site may be recognized as an epitope during naturally occurring infections.
Collapse
Affiliation(s)
- Hirokazu Kimura
- Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan; Department of Microbiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanagawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan.
| | - Koo Nagasawa
- Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan
| | - Ryusuke Kimura
- Faculty of Pharmacy, Takasaki University of Health and Welfare, 37-1 Nakaoruimachi, Takasaki-shi, Gunma 370-0033, Japan
| | - Hiroyuki Tsukagoshi
- Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
| | - Yuki Matsushima
- Kawasaki City Institute for Public Health, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-0821, Japan
| | - Kiyotaka Fujita
- School of Medical Technology, Faculty of Health Science, Gumma Paz College, 1-7-1 Tonyamachi, Takasaki-shi, Gunma 370-0006, Japan
| | - Eiko Hirano
- Fukui Prefectural Institute of Public Health and Environmental Science, 39-4 Harame-cho, Fukui-shi, Fukui 910-8851, Japan
| | - Naruhiko Ishiwada
- Division of Infection Control and Prevention, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan
| | - Takako Misaki
- Kawasaki City Institute for Public Health, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-0821, Japan
| | - Kazunori Oishi
- Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan
| | - Makoto Kuroda
- Pathogen Genomics Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
| | - Akihide Ryo
- Department of Microbiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanagawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan
| |
Collapse
|
|
18
|
Saikusa M, Kawakami C, Nao N, Takeda M, Usuku S, Sasao T, Nishimoto K, Toyozawa T. 180-Nucleotide Duplication in the G Gene of Human metapneumovirus A2b Subgroup Strains Circulating in Yokohama City, Japan, since 2014. Front Microbiol 2017; 8:402. [PMID: 28352258 PMCID: PMC5348506 DOI: 10.3389/fmicb.2017.00402] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Accepted: 02/27/2017] [Indexed: 12/03/2022] Open
Abstract
Human metapneumovirus (HMPV), a member of the family Paramyxoviridae, was first isolated in 2001. Seroepidemiological studies have shown that HMPV has been a major etiological agent of acute respiratory infections in humans for more than 50 years. Molecular epidemiological, genetic, and antigenetic evolutionary studies of HMPV will strengthen our understanding of the epidemic behavior of the virus and provide valuable insight for the control of HMPV and the development of vaccines and antiviral drugs against HMPV infection. In this study, the nucleotide sequence of and genetic variations in the G gene were analyzed in HMPV strains prevalent in Yokohama City, in the Kanto area, Japan, between January 2013 and June 2016. As a part of the National Epidemiological Surveillance of Infectious Diseases, Japan, 1308 clinical specimens (throat swabs, nasal swabs, nasal secretions, and nasal aspirate fluids) collected at 24 hospitals or clinics in Yokohama City were screened for 15 major respiratory viruses with a multiplex reverse transcription–PCR assay. HMPV was detected in 91 specimens, accounting for 7.0% of the total specimens, and the nucleotide sequences of the G genes of 84 HMPV strains were determined. Among these 84 strains, 6, 43, 10, and 25 strains were classified into subgroups A2a, A2b, B1, and B2, respectively. Approximately half the HMPV A2b subgroup strains detected since 2014 had a 180-nucleotide duplication (180nt-dup) in the G gene and clustered on a phylogenic tree with four classical 180nt-dup-lacking HMPV A2b strains prevalent between 2014 and 2015. The 180nt-dup causes a 60-amino-acid duplication (60aa-dup) in the G protein, creating 23–25 additional potential acceptor sites for O-linked sugars. Our data suggest that 180nt-dup occurred between 2011 and 2013 and that HMPV A2b strains with 180nt-dup (A2b180nt-dup HMPV) became major epidemic strains within 3 years. The detailed mechanism by which the A2b180nt-dup HMPV strains gained an advantage that allowed their efficient spread in the community and the effects of 60aa-dup on HMPV virulence must be clarified.
Collapse
Affiliation(s)
- Miwako Saikusa
- Yokohama City Institute of Public Health Yokohama, Japan
| | | | - Naganori Nao
- Department of Virology III, National Institute of Infectious Diseases Musashimurayama, Japan
| | - Makoto Takeda
- Department of Virology III, National Institute of Infectious Diseases Musashimurayama, Japan
| | - Shuzo Usuku
- Yokohama City Institute of Public Health Yokohama, Japan
| | | | | | | |
Collapse
|
|
19
|
Lam TTY, Zhu H, Guan Y, Holmes EC. Genomic Analysis of the Emergence, Evolution, and Spread of Human Respiratory RNA Viruses. Annu Rev Genomics Hum Genet 2016; 17:193-218. [PMID: 27216777 DOI: 10.1146/annurev-genom-083115-022628] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The emergence and reemergence of rapidly evolving RNA viruses-particularly those responsible for respiratory diseases, such as influenza viruses and coronaviruses-pose a significant threat to global health, including the potential of major pandemics. Importantly, recent advances in high-throughput genome sequencing enable researchers to reveal the genomic diversity of these viral pathogens at much lower cost and with much greater precision than they could before. In particular, the genome sequence data generated allow inferences to be made on the molecular basis of viral emergence, evolution, and spread in human populations in real time. In this review, we introduce recent computational methods that analyze viral genomic data, particularly in combination with metadata such as sampling time, geographic location, and virulence. We then outline the insights these analyses have provided into the fundamental patterns and processes of evolution and emergence in human respiratory RNA viruses, as well as the major challenges in such genomic analyses.
Collapse
Affiliation(s)
- Tommy T-Y Lam
- State Key Laboratory of Emerging Infectious Diseases and Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong, China; , ,
- Joint Influenza Research Center and Joint Institute of Virology, Shantou University Medical College, Shantou 515041, China
- State Key Laboratory of Emerging Infectious Diseases (HKU-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen 518112, China
| | - Huachen Zhu
- State Key Laboratory of Emerging Infectious Diseases and Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong, China; , ,
- Joint Influenza Research Center and Joint Institute of Virology, Shantou University Medical College, Shantou 515041, China
- State Key Laboratory of Emerging Infectious Diseases (HKU-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen 518112, China
| | - Yi Guan
- State Key Laboratory of Emerging Infectious Diseases and Centre of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong, China; , ,
- Joint Influenza Research Center and Joint Institute of Virology, Shantou University Medical College, Shantou 515041, China
- State Key Laboratory of Emerging Infectious Diseases (HKU-Shenzhen Branch), Shenzhen Third People's Hospital, Shenzhen 518112, China
- Department of Microbiology, Guangxi Medical University, Nanning 530021, China
| | - Edward C Holmes
- Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia;
| |
Collapse
|
|
20
|
Do LAH, Wilm A, van Doorn HR, Lam HM, Sim S, Sukumaran R, Tran AT, Nguyen BH, Tran TTL, Tran QH, Vo QB, Dac NAT, Trinh HN, Nguyen TTH, Binh BTL, Le K, Nguyen MT, Thai QT, Vo TV, Ngo NQM, Dang TKH, Cao NH, Tran TV, Ho LV, Farrar J, de Jong M, Chen S, Nagarajan N, Bryant JE, Hibberd ML. Direct whole-genome deep-sequencing of human respiratory syncytial virus A and B from Vietnamese children identifies distinct patterns of inter- and intra-host evolution. J Gen Virol 2016; 96:3470-3483. [PMID: 26407694 DOI: 10.1099/jgv.0.000298] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Human respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in children ,2 years of age. Little is known about RSV intra-host genetic diversity over the course of infection or about the immune pressures that drive RSV molecular evolution. We performed whole-genome deep-sequencing on 53 RSV-positive samples (37 RSV subgroup A and 16 RSV subgroup B) collected from the upper airways of hospitalized children in southern Vietnam over two consecutive seasons. RSV A NA1 and RSV B BA9 were the predominant genotypes found in our samples, consistent with other reports on global RSV circulation during the same period. For both RSV A and B, the M gene was the most conserved, confirming its potential as a target for novel therapeutics. The G gene was the most variable and was the only gene under detectable positive selection. Further, positively selected sites inG were found in close proximity to and in some cases overlapped with predicted glycosylation motifs, suggesting that selection on amino acid glycosylation may drive viral genetic diversity. We further identified hotspots and coldspots of intra-host genetic diversity in the RSV genome, some of which may highlight previously unknown regions of functional importance.
Collapse
Affiliation(s)
- Lien Anh Ha Do
- Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam
| | - Andreas Wilm
- Genome Institute of Singapore, Genome Building, 138672 Singapore
| | - H Rogier van Doorn
- Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.,Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
| | - Ha Minh Lam
- Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam
| | - Shuzhen Sim
- Genome Institute of Singapore, Genome Building, 138672 Singapore
| | - Rashmi Sukumaran
- Genome Institute of Singapore, Genome Building, 138672 Singapore
| | - Anh Tuan Tran
- Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam
| | - Bach Hue Nguyen
- Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam
| | - Thi Thu Loan Tran
- Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam
| | - Quynh Huong Tran
- Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam
| | - Quoc Bao Vo
- Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam
| | | | - Hong Nhien Trinh
- Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam
| | | | - Bao Tinh Le Binh
- Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam
| | - Khanh Le
- Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam
| | - Minh Tien Nguyen
- Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam
| | - Quang Tung Thai
- Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam
| | - Thanh Vu Vo
- Children's Hospital 1, Ward 10, District 10, Ho Chi Minh City, Vietnam
| | | | - Thi Kim Huyen Dang
- Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam
| | - Ngoc Huong Cao
- Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam
| | - Thu Van Tran
- Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam
| | - Lu Viet Ho
- Children's Hospital 2, Ben Nghe Ward, District 1, Ho Chi Minh City, Vietnam
| | - Jeremy Farrar
- Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam
| | - Menno de Jong
- Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.,Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.,Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Swaine Chen
- Genome Institute of Singapore, Genome Building, 138672 Singapore
| | | | - Juliet E Bryant
- Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.,Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
| | - Martin L Hibberd
- Genome Institute of Singapore, Genome Building, 138672 Singapore
| |
Collapse
|
|
21
|
Owor BE, Masankwa GN, Mwango LC, Njeru RW, Agoti CN, Nokes DJ. Human metapneumovirus epidemiological and evolutionary patterns in Coastal Kenya, 2007-11. BMC Infect Dis 2016; 16:301. [PMID: 27316548 PMCID: PMC4912817 DOI: 10.1186/s12879-016-1605-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Accepted: 06/01/2016] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Human metapneumovirus (HMPV) is an important global cause of severe acute respiratory infections in young children and the elderly. The epidemiology of HMPV in sub-Saharan Africa is poorly described and factors that allow its recurrent epidemics in communities not understood. METHODS We undertook paediatric inpatient surveillance for HMPV in Kilifi County Hospital (KCH) of Coastal Kenya between 2007 and 2011. Nasopharyngeal samples collected from children aged 1 day-59 months admitted with severe or very severe pneumonia, were tested for HMPV using real-time polymerase chain reaction (RT-PCR). Partial nucleotide sequences of the attachment (G) and fusion (F) surface proteins of positive samples were determined and phylogenetically analyzed. RESULTS HMPV was detected in 4.8 % (160/3320) of children [73.8 % (118/160) of these less than one year of age], ranging between 2.9 and 8.8 % each year over the 5 years of study. HMPV infections were seasonal in occurrence, with cases predominant in the months of November through April. These months frequently coincided with low rainfall, high temperature and low relative humidity in the location. Phylogenetic analysis of partial F and G sequences revealed three subgroups of HMPV, A2 (74 %, 91/123), B1 (3.2 %, 4/123) and B2 (22.8 %, 28/123) in circulation, with subgroup A2 predominant in majority of the epidemic seasons. Comparison of G sequences (local and global) provided a greater phylogenetic resolution over comparison of F sequences and indicated presence of probable multiple G antigenic variants within the subgroups due to differences in amino acid sequence, encoded protein length and glycosylation patterns. CONCLUSION The present study reveals HMPV is an important seasonal contributor to respiratory disease hospitalization in coastal Kenya, with an evolutionary pattern closely relating to that of respiratory syncytial virus.
Collapse
Affiliation(s)
- Betty E Owor
- Kenya Medical Research Institute (KEMRI) -Wellcome Trust Research Programme, Kilifi, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya.
| | - Geoffrey N Masankwa
- Kenya Medical Research Institute (KEMRI) -Wellcome Trust Research Programme, Kilifi, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Lilian C Mwango
- Kenya Medical Research Institute (KEMRI) -Wellcome Trust Research Programme, Kilifi, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Regina W Njeru
- Kenya Medical Research Institute (KEMRI) -Wellcome Trust Research Programme, Kilifi, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya
| | - Charles N Agoti
- Kenya Medical Research Institute (KEMRI) -Wellcome Trust Research Programme, Kilifi, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya.,Department of Biomedical Sciences, Pwani University, Kilifi, Kenya
| | - D James Nokes
- Kenya Medical Research Institute (KEMRI) -Wellcome Trust Research Programme, Kilifi, KEMRI Centre for Geographic Medicine Research - Coast, Kilifi, Kenya. .,School of Life Sciences and WIDER, University of Warwick, Coventry, UK.
| |
Collapse
|
|
22
|
Molecular evolution of the fusion protein gene in human respiratory syncytial virus subgroup A. INFECTION GENETICS AND EVOLUTION 2016; 43:398-406. [PMID: 27291709 DOI: 10.1016/j.meegid.2016.06.019] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/01/2016] [Revised: 06/01/2016] [Accepted: 06/07/2016] [Indexed: 12/18/2022]
Abstract
We studied the molecular evolution of the fusion protein (F) gene in the human respiratory syncytial virus subgroup A (HRSV-A). We performed time-scaled phylogenetic analyses using the Bayesian Markov chain Monte Carlo (MCMC) method. We also conducted genetic distance (p-distance), positive/negative selection, and Bayesian skyline plot analyses. Furthermore, we mapped the amino acid substitutions of the protein. The MCMC-constructed tree indicated that the HRSV F gene diverged from the bovine RSV (BRSV) gene approximately 550years ago and had a relatively low substitution rate (7.59×10(-4) substitutions/site/year). Moreover, a common ancestor of HRSV-A and -B diverged approximately 280years ago, which has since formed four distinct clusters. The present HRSV-A strains were assigned six genotypes based on F gene sequences and attachment glycoprotein gene sequences. The present strains exhibited high F gene sequence similarity values and low genetic divergence. No positive selection sites were identified; however, 50 negative selection sites were identified. F protein amino acid substitutions at 17 sites were distributed in the F protein. The effective population size of the gene has remained relatively constant, but the population size of the prevalent genotype (GA2) has increased in the last 10years. These results suggest that the HRSV-AF gene has evolved independently and formed some genotypes.
Collapse
|
|
23
|
Tuan TA, Thanh TT, Hai NTT, Tinh LBB, Kim LTN, Do LAH, Chinh B'Krong NTT, Tham NT, Hang VTT, Merson L, Farrar J, Thuong TC, de Jong MD, Schultsz C, van Doorn HR. Characterization of hospital and community-acquired respiratory syncytial virus in children with severe lower respiratory tract infections in Ho Chi Minh City, Vietnam, 2010. Influenza Other Respir Viruses 2016; 9:110-9. [PMID: 25702707 PMCID: PMC4415695 DOI: 10.1111/irv.12307] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/12/2015] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Human respiratory syncytial virus (RSV) is an important community and nosocomial pathogen in developed countries but data regarding the importance of RSV in developing countries are relatively scarce. METHODS During a 1-year surveillance study in 2010, we took serial samples from children admitted to the Emergency Unit of the Respiratory Ward of Children's Hospital 1 in Ho Chi Minh City, Vietnam. RSV was detected within 72 hours of admission to the ward in 26% (376/1439; RSV A: n = 320; RSV B: n = 54; and RSV A and B: n = 2). Among those negative in the first 72 hours after admission, 6.6% (25/377) acquired nosocomial RSV infection during hospitalization (RSV A: n = 22; and RSV B: n = 3). RESULTS Children with nosocomial RSV infection were younger (P = 0.001) and had a longer duration of hospitalization (P < 0.001). The rate of incomplete recovery among children with nosocomial RSV infection was significantly higher than among those without (P < 0.001). Phylogenetic analysis of partial G gene sequences obtained from 79% (316/401) of positive specimens revealed the co-circulation of multiple genotypes with RSV A NA1 being predominant (A NA1: n = 275; A GA5: n = 5; B BA3: n = 3; B BA9: n = 26; and B BA10: n = 7). The RSV A GA5 and RSV B BA3 genotypes have not been reported from Vietnam, previously. CONCLUSION Besides emphasizing the importance of RSV as a cause of respiratory infection leading to hospitalization in young children and as a nosocomial pathogen, data from this study extend our knowledge on the genetic diversity of RSV circulating in Vietnam.
Collapse
|
|
24
|
Trento A, Ábrego L, Rodriguez-Fernandez R, González-Sánchez MI, González-Martínez F, Delfraro A, Pascale JM, Arbiza J, Melero JA. Conservation of G-Protein Epitopes in Respiratory Syncytial Virus (Group A) Despite Broad Genetic Diversity: Is Antibody Selection Involved in Virus Evolution? J Virol 2015; 89:7776-85. [PMID: 25995258 PMCID: PMC4505632 DOI: 10.1128/jvi.00467-15] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2015] [Accepted: 05/11/2015] [Indexed: 11/20/2022] Open
Abstract
UNLABELLED Worldwide G-glycoprotein phylogeny of human respiratory syncytial virus (hRSV) group A sequences revealed diversification in major clades and genotypes over more than 50 years of recorded history. Multiple genotypes cocirculated during prolonged periods of time, but recent dominance of the GA2 genotype was noticed in several studies, and it is highlighted here with sequences from viruses circulating recently in Spain and Panama. Reactivity of group A viruses with monoclonal antibodies (MAbs) that recognize strain-variable epitopes of the G glycoprotein failed to correlate genotype diversification with antibody reactivity. Additionally, no clear correlation was found between changes in strain-variable epitopes and predicted sites of positive selection, despite both traits being associated with the C-terminal third of the G glycoprotein. Hence, our data do not lend support to the proposed antibody-driven selection of variants as a major determinant of hRSV evolution. Other alternative mechanisms are considered to account for the high degree of hRSV G-protein variability. IMPORTANCE An unusual characteristic of the G glycoprotein of human respiratory syncytial virus (hRSV) is the accumulation of nonsynonymous (N) changes at higher rates than synonymous (S) changes, reaching dN/dS values at certain sites predictive of positive selection. Since these sites cluster preferentially in the C-terminal third of the G protein, like certain epitopes recognized by murine antibodies, it was proposed that immune (antibody) selection might be driving the apparent positive selection, analogous to the antigenic drift observed in the influenza virus hemagglutinin (HA). However, careful antigenic and genetic comparison of the G glycoprotein does not provide evidence of antigenic drift in the G molecule, in agreement with recently published data which did not indicate antigenic drift in the G protein with human sera. Alternative explanations to the immune-driven selection hypothesis are offered to account for the high level of G-protein genetic diversity highlighted in this study.
Collapse
Affiliation(s)
- Alfonsina Trento
- Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid, Spain CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
| | - Leyda Ábrego
- Departamento de Investigación en Virología, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panamá, Panama
| | | | | | | | - Adriana Delfraro
- Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Juan M Pascale
- Departamento de Investigación en Virología, Instituto Conmemorativo Gorgas de Estudios de la Salud, Panamá, Panama
| | - Juan Arbiza
- Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - José A Melero
- Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid, Spain CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
| |
Collapse
|
|
25
|
Sequencing and analysis of globally obtained human respiratory syncytial virus A and B genomes. PLoS One 2015; 10:e0120098. [PMID: 25793751 PMCID: PMC4368745 DOI: 10.1371/journal.pone.0120098] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Accepted: 01/19/2015] [Indexed: 11/19/2022] Open
Abstract
Background Human respiratory syncytial virus (RSV) is the leading cause of respiratory tract infections in children globally, with nearly all children experiencing at least one infection by the age of two. Partial sequencing of the attachment glycoprotein gene is conducted routinely for genotyping, but relatively few whole genome sequences are available for RSV. The goal of our study was to sequence the genomes of RSV strains collected from multiple countries to further understand the global diversity of RSV at a whole-genome level. Methods We collected RSV samples and isolates from Mexico, Argentina, Belgium, Italy, Germany, Australia, South Africa, and the USA from the years 1998-2010. Both Sanger and next-generation sequencing with the Illumina and 454 platforms were used to sequence the whole genomes of RSV A and B. Phylogenetic analyses were performed using the Bayesian and maximum likelihood methods of phylogenetic inference. Results We sequenced the genomes of 34 RSVA and 23 RSVB viruses. Phylogenetic analysis showed that the RSVA genome evolves at an estimated rate of 6.72 × 10-4 substitutions/site/year (95% HPD 5.61 × 10-4 to 7.6 × 10-4) and for RSVB the evolutionary rate was 7.69 × 10-4 substitutions/site/year (95% HPD 6.81 × 10-4 to 8.62 × 10-4). We found multiple clades co-circulating globally for both RSV A and B. The predominant clades were GA2 and GA5 for RSVA and BA for RSVB. Conclusions Our analyses showed that RSV circulates on a global scale with the same predominant clades of viruses being found in countries around the world. However, the distribution of clades can change rapidly as new strains emerge. We did not observe a strong spatial structure in our trees, with the same three main clades of RSV co-circulating globally, suggesting that the evolution of RSV is not strongly regionalized.
Collapse
|
|
26
|
Abstract
Human metapneumovirus (hMPV) and respiratory syncytial virus, its close family member, are two major causes of lower respiratory tract infection in the paediatric population. hMPV is also a common cause of worldwide morbidity and mortality in immunocompromised patients and older adults. Repeated infections occur often, demonstrating a heavy medical burden. However, there is currently no hMPV-specific prevention treatment. This review focuses on the current literature on hMPV vaccine development. We believe that a better understanding of the role(s) of viral proteins in host responses might lead to efficient prophylactic vaccine development.
Collapse
Affiliation(s)
- J Ren
- 1Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA
| | - T Phan
- 1Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA
| | - X Bao
- 2Institute for Translational Science, University of Texas Medical Branch, Galveston, TX, USA 3Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA 1Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA
| |
Collapse
|
|
27
|
Prachayangprecha S, Schapendonk CME, Koopmans MP, Osterhaus ADME, Schürch AC, Pas SD, van der Eijk AA, Poovorawan Y, Haagmans BL, Smits SL. Exploring the potential of next-generation sequencing in detection of respiratory viruses. J Clin Microbiol 2014; 52:3722-3730. [PMID: 25100822 PMCID: PMC4187785 DOI: 10.1128/jcm.01641-14] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Accepted: 07/31/2014] [Indexed: 12/23/2022] Open
Abstract
Efficient detection of human respiratory viral pathogens is crucial in the management of patients with acute respiratory tract infection. Sequence-independent amplification of nucleic acids combined with next-generation sequencing technology and bioinformatics analyses is a promising strategy for identifying pathogens in clinical and public health settings. It allows the characterization of hundreds of different known pathogens simultaneously and of novel pathogens that elude conventional testing. However, major hurdles for its routine use exist, including cost, turnaround time, and especially sensitivity of the assay, as the detection limit is dependent on viral load, host genetic material, and sequencing depth. To obtain insights into these aspects, we analyzed nasopharyngeal aspirates from a cohort of 81 Thai children with respiratory disease for the presence of respiratory viruses using a sequence-independent next-generation sequencing approach and routinely used diagnostic real-time reverse transcriptase PCR (real-time RT-PCR) assays. With respect to the detection of rhinovirus and human metapneumovirus, the next-generation sequencing approach was at least as sensitive as diagnostic real-time RT-PCR in this small cohort, whereas for bocavirus and enterovirus, next-generation sequencing was less sensitive than real-time RT-PCR. The advantage of the sequencing approach over real-time RT-PCR was the immediate availability of virus-typing information. Considering the development of platforms capable of generating more output data at declining costs, next-generation sequencing remains of interest for future virus diagnosis in clinical and public health settings and certainly as an additional tool when screening results from real-time RT-PCR are negative.
Collapse
Affiliation(s)
- Slinporn Prachayangprecha
- Center of Excellence in Clinical Virology, Department of Pediatrics, Chulalongkorn University and Hospital, Bangkok, Thailand
| | | | - Marion P Koopmans
- Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands Virology Division, Centre for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment, Bilthoven, the Netherlands
| | - Albert D M E Osterhaus
- Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands Viroclinics Biosciences, Rotterdam, the Netherlands
| | - Anita C Schürch
- Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Suzan D Pas
- Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
| | | | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Department of Pediatrics, Chulalongkorn University and Hospital, Bangkok, Thailand
| | - Bart L Haagmans
- Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Saskia L Smits
- Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands Viroclinics Biosciences, Rotterdam, the Netherlands
| |
Collapse
|
|
28
|
Hasegawa K, Mansbach JM, Camargo CA. Infectious pathogens and bronchiolitis outcomes. Expert Rev Anti Infect Ther 2014; 12:817-28. [PMID: 24702592 DOI: 10.1586/14787210.2014.906901] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Bronchiolitis is a common early childhood illness and an important cause of morbidity, it is the number one cause of hospitalization among US infants. Bronchiolitis is also an active area of research, and recent studies have advanced our understanding of this illness. Although it has long been the conventional wisdom that the infectious etiology of bronchiolitis does not affect outcomes, a growing number of studies have linked specific pathogens of bronchiolitis (e.g., rhinovirus) to short- and long-term outcomes, such as future risk of developing asthma. The authors review the advent of molecular diagnostic techniques that have demonstrated diverse pathogens in bronchiolitis, and they review recent studies on the complex link between infectious pathogens of bronchiolitis and the development of childhood asthma.
Collapse
Affiliation(s)
- Kohei Hasegawa
- Department of Emergency Medicine (KH, CAC), Boston, MA, USA
| | | | | |
Collapse
|
|
29
|
Horthongkham N, Athipanyasilp N, Sirijatuphat R, Assanasen S, Sutthent R. Prevalence and molecular characterization of human metapneumovirus in influenza a negative sample in Thailand. J Clin Lab Anal 2014; 28:398-404. [PMID: 24652781 PMCID: PMC6807631 DOI: 10.1002/jcla.21700] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Accepted: 10/02/2013] [Indexed: 11/22/2022] Open
Abstract
Background Human metapneumovirus (hMPV) causes respiratory tract infection in influenza‐like illness. The role of hMPV infections in all age groups in Thailand has not yet been investigated. Thus, the objective of this study was to determine prevalence of hMPV infection in all age groups in Thailand during 2011. Methods A total of 1,184 nasopharyngeal washes were collected from hospitalized patients and sent to the Department of Microbiology, Siriraj Hospital, for influenza A virus detection. Real‐time polymerase chain reaction (PCR) was used to detect hMPV infection. Partially, F gene from hMPV positive samples were sequenced and used for genotyping by phylogenetic tree analysis. Results The prevalence of hMPV for all age groups was 6.3%. The highest prevalence of hMPV infection was in children aged <2 years. Of 71 hMPV‐positive patients, three (4.2%) were coinfected with respiratory syncytial virus (RSV), two with rhinovirus (2.8%), one with coronavirus (1.4%), and one with RSV and adenovirus (1.4%). Phylogenetic analysis of F gene revealed that 96.8% of hMPV detected was subgenotype B1, 1.6% was sublineage A2a, and 1.6% was A2b. Genetic variation of F gene was much conserved. Conclusion We demonstrated the prevalence of hMPV subgenotype B1 circulating in Thailand during 2011.
Collapse
Affiliation(s)
- Navin Horthongkham
- Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | | | | | | | | |
Collapse
|
|
30
|
Robinson MJ, Tan CS, Fenwick F, Chambers CJ, Routledge EG, Toms GL. Generation and epitope mapping of a sub-group cross-reactive anti-respiratory syncytial virus G glycoprotein monoclonal antibody which is protective in vivo. J Med Virol 2014; 86:1267-77. [PMID: 24415460 DOI: 10.1002/jmv.23881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2013] [Indexed: 11/07/2022]
Abstract
Passively administered antibodies to conserved epitopes on the attachment (G) glycoprotein of human respiratory syncytial virus (hRSV) have potential in the immunoprophylaxis of human infections. This study set out to generate monoclonal antibodies (MAbs) recognizing all prevalent lineages of HRSV and capable of immunoprophylaxis in mice. Two murine MAbs of broad specificity for prevalent virus strains were generated by immunization of mice with hRSV of sub-group A followed by selection of hybridomas on recombinant G glycoprotein from a sub-group B virus. The anti-G hybridomas generated secreted antibody of high affinity but negligible neutralizing capacity one of which was tested in mice and found to be protective against live virus challenge. Western blotting and partial epitope mapping on transiently expressed G-glycoprotein fragments indicate that these antibodies recognize a complex epitope on the protein backbone of the molecule involving residues both C'- and N-terminal to the central conserved motif.
Collapse
Affiliation(s)
- Mark J Robinson
- Institute of Cellular Medicine, The Medical School, Newcastle upon Tyne, United Kingdom
| | | | | | | | | | | |
Collapse
|
|
31
|
Palavecino CE, Céspedes PF, Gómez RS, Kalergis AM, Bueno SM. Immunization with a recombinant bacillus Calmette-Guerin strain confers protective Th1 immunity against the human metapneumovirus. THE JOURNAL OF IMMUNOLOGY 2013; 192:214-23. [PMID: 24319265 DOI: 10.4049/jimmunol.1300118] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Along with the human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, owing to an inefficient immunological memory, hMPV infection provides limited immune protection against reinfection. Furthermore, hMPV can induce an inadequate Th2 type immune response that causes severe lung inflammation, leading to airway obstruction. Similar to hRSV, it is likely that an effective clearance of hMPV would require a balanced Th1 type immunity by the host, involving the activation of IFN-γ-secreting T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which has been used in newborns for many decades and in several countries as a tuberculosis vaccine. We have previously shown that immunization with BCG strains expressing hRSV Ags can induce an efficient immune response that protects against this virus. In this study, we show that immunization with rBCG strains expressing the phosphoprotein from hMPV also can induce protective Th1 immunity. Mice immunized with rBCG were protected against weight loss, airway inflammation, and viral replication in the lungs after hMPV infection. Our rBCG vaccine also induced the activation of hMPV-specific T cells producing IFN-γ and IL-2, which could protect from hMPV infection when transferred to recipient mice. These data strongly support the notion that rBCG induces protective Th1 immunity and could be considered as an efficient vaccine against hMPV.
Collapse
Affiliation(s)
- Christian E Palavecino
- Instituto Milenio en Inmunología e Inmunoterapia, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile
| | | | | | | | | |
Collapse
|
|
32
|
Tedcastle A, Fenwick F, Robinson M, Toms G. Immunogenicity in mice of human metapneumovirus with a truncated SH glycoprotein. J Med Virol 2013; 86:547-57. [DOI: 10.1002/jmv.23731] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/12/2013] [Indexed: 11/12/2022]
Affiliation(s)
- A.B. Tedcastle
- The Institute of Cellular Medicine; The University of Newcastle upon Tyne; Newcastle upon Tyne United Kingdom
| | - F. Fenwick
- The Institute of Cellular Medicine; The University of Newcastle upon Tyne; Newcastle upon Tyne United Kingdom
| | - M.J. Robinson
- The Institute of Cellular Medicine; The University of Newcastle upon Tyne; Newcastle upon Tyne United Kingdom
| | - G.L. Toms
- The Institute of Cellular Medicine; The University of Newcastle upon Tyne; Newcastle upon Tyne United Kingdom
| |
Collapse
|
|
33
|
Biswas D, Yadav K, Borkakoty B, Mahanta J. Molecular characterization of human respiratory syncytial virus NA1 and GA5 genotypes detected in Assam in northeast India, 2009-2012. J Med Virol 2013; 85:1639-44. [DOI: 10.1002/jmv.23636] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2013] [Indexed: 11/09/2022]
Affiliation(s)
- Dipankar Biswas
- Regional Medical Research Centre; NE Region (Indian Council of Medical Research); Dibrugarh; Assam; India
| | - Kaushal Yadav
- Regional Medical Research Centre; NE Region (Indian Council of Medical Research); Dibrugarh; Assam; India
| | - Biswajyoti Borkakoty
- Regional Medical Research Centre; NE Region (Indian Council of Medical Research); Dibrugarh; Assam; India
| | - Jagadish Mahanta
- Regional Medical Research Centre; NE Region (Indian Council of Medical Research); Dibrugarh; Assam; India
| |
Collapse
|
|
34
|
Abstract
PURPOSE OF REVIEW The first era in the discoveries of respiratory viruses occured between 1933 and 1965 when influenza virus, enteroviruses, adenovirus, respiratory syncytial virus, rhinovirus, parainfluenza virus and coronavirus (CoV) were found by virus culture. In the 1990s, the development of high throughput viral detection and diagnostics instruments increased diagnostic sensitivity and enabled the search for new viruses. This article briefly reviews the clinical significance of newly discovered respiratory viruses. RECENT FINDINGS In 2001, the second era in the discoveries of respiratory viruses began, and several new respiratory viruses and their subgroups have been found: human metapneumovirus, CoVs NL63 and HKU1, human bocavirus and human rhinovirus C and D groups. SUMMARY Currently, a viral cause of pediatric respiratory illness is identifiable in up to 95% of cases, but the detection rates decrease steadily by age, to 30-40% in the elderly. The new viruses cause respiratory illnesses such as common cold, bronchitis, bronchiolitis, exacerbations of asthma and chronic obstructive pulmonary disease and pneumonia. Rarely, acute respiratory failure may occur. The clinical role of other new viruses, KI and WU polyomaviruses and the torque teno virus, as respiratory pathogens is not clear.
Collapse
|
|
35
|
Cuthill JH, Charleston MA. A simple model explains the dynamics of preferential host switching among mammal RNA viruses. Evolution 2013; 67:980-90. [PMID: 23550750 PMCID: PMC7202234 DOI: 10.1111/evo.12064] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
A growing number of studies support a tendency toward preferential host switching, by parasites and pathogens, over relatively short phylogenetic distances. This suggests that a host switch is more probable if a potential host is closely related to the original host than if it is a more distant relative. However, despite its importance for the health of humans, livestock, and wildlife, the detailed dynamics of preferential host switching have, so far, been little studied. We present an empirical test of two theoretical models of preferential host switching, using observed phylogenetic distributions of host species for RNA viruses of three mammal orders (primates, carnivores, and ungulates). The analysis focuses on multihost RNA virus species, because their presence on multiple hosts and their estimated ages of origin indicate recent host switching. Approximate Bayesian computation was used to compare observed phylogenetic distances between hosts with those simulated under the theoretical models. The results support a decreasing sigmoidal model of preferential host switching, with a strong effect from increasing phylogenetic distance, on all three studied host phylogenies. This suggests that the dynamics of host switching are fundamentally similar for RNA viruses of different mammal orders and, potentially, a wider range of coevolutionary systems.
Collapse
Affiliation(s)
- Jennifer Hoyal Cuthill
- School of Information Technologies, University of Sydney, Sydney, New South Wales 2006, Australia.
| | | |
Collapse
|
|
36
|
Yang CF, Wang CK, Tollefson SJ, Lintao LD, Liem A, Chu M, Williams JV. Human metapneumovirus G protein is highly conserved within but not between genetic lineages. Arch Virol 2013; 158:1245-52. [PMID: 23385328 DOI: 10.1007/s00705-013-1622-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Accepted: 12/17/2012] [Indexed: 11/30/2022]
Abstract
Human metapneumovirus (HMPV) is an important cause of acute respiratory illnesses in children. HMPV encodes two major surface glycoproteins, fusion (F) and glycoprotein (G). The function of G has not been fully established, though it is dispensable for in vitro and in vivo replication. We analyzed 87 full-length HMPV G sequences from isolates collected over 20 years. The G sequences fell into four subgroups with a mean 63 % amino acid identity (minimum 29 %). The length of G varied from 217 to 241 residues. Structural features such as proline content and N- and O-glycosylation sites were present in all strains but quite variable between subgroups. There was minimal drift within the subgroups over 20 years. The estimated time to the most recent common ancestor was 215 years. HMPV G was conserved within lineages over 20 years, suggesting functional constraints on diversity. However, G was poorly conserved between subgroups, pointing to potentially distinct roles for G among different viral lineages.
Collapse
|
|
37
|
Paiva TM, Ishida MA, Benega MA, Constantino CRA, Silva DBB, Santos KCO, Oliveira MI, Barbosa HA, Carvalhanas TRMP, Schuck-Paim C, Alonso WJ. Shift in the timing of respiratory syncytial virus circulation in a subtropical megalopolis: implications for immunoprophylaxis. J Med Virol 2013; 84:1825-30. [PMID: 22997087 DOI: 10.1002/jmv.23347] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Respiratory syncytial virus (RSV) is the most common cause of severe respiratory infections worldwide, and an important cause of childhood bronchiolitis, pneumonia, and mortality. Although prevention of RSV infection by immunoprophylaxis with palivizumab has proved effective, a precise understanding of the timing of RSV outbreaks is necessary to ensure that infants are protected when RSV is circulating. In this study a consistent shift in the seasonal patterns of RSV circulation in southeast Brazil (São Paulo) is reported based on the analysis of 15 years of viral surveillance. Surveillance was conducted from 1996 to 2010 and involved the collection of samples from children with symptoms of acute respiratory infection. Putative changes in school terms, in the proportion of RSV genotypes infecting children and in the seasonal dynamics of several climatic parameters during the period were also investigated. The results revealed a progression in the timing of RSV seasons, with a shift in the onset and peak of RSV epidemics from 2007 onwards. Although lower rainfall and temperatures were associated with the onset of outbreaks, there was no evidence of changes in climate, school terms or in the relative proportion of genotypes in the period analyzed. These findings have direct implications for improving the prophylactic use of palivizumab, and stress the importance of fine tuning prophylaxis with recent surveillance data. In the case of São Paulo, palivizumab prophylaxis should be initiated earlier than suggested currently. Similar adjustments may be necessary in other regions.
Collapse
Affiliation(s)
- Terezinha M Paiva
- Center of Respiratory Diseases, Adolfo Lutz Institute, São Paulo, Brazil
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Melero JA, Moore ML. Influence of respiratory syncytial virus strain differences on pathogenesis and immunity. Curr Top Microbiol Immunol 2013; 372:59-82. [PMID: 24362684 DOI: 10.1007/978-3-642-38919-1_3] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Molecular epidemiology studies have provided convincing evidence of antigenic and sequence variability among respiratory syncytial virus (RSV) isolates. Circulating viruses have been classified into two antigenic groups (A and B) that correlate with well-delineated genetic groups. Most sequence and antigenic differences (both inter- and intra-groups) accumulate in two hypervariable segments of the G-protein gene. Sequences of the G gene have been used for phylogenetic analyses. These studies have shown a worldwide distribution of RSV strains with both local and global replacement of dominant viruses with time. Although data are still limited, there is evidence that strain variation may contribute to differences in pathogenicity. In addition, there is some but limited evidence that RSV variation may be, at least partially, immune (antibody) driven. However, there is the paradox in RSV that, in contrast to other viruses (e.g., influenza viruses) the epitopes recognized by the most effective RSV-neutralizing antibodies are highly conserved. In contrast, antibodies that recognize strain-specific epitopes are poorly neutralizing. It is likely that this apparent contradiction is due to the lack of a comprehensive knowledge of the duration and specificities of the human antibody response against RSV antigens. Since there are some data supporting a group- (or clade-) specific antibody response after a primary infection in humans, it may be wise to consider the incorporation of strains representative of groups A and B (or their antigens) in future RSV vaccine development.
Collapse
Affiliation(s)
- José A Melero
- Unidad de Biología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain,
| | | |
Collapse
|
|
39
|
Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology. PLoS One 2012; 7:e51439. [PMID: 23236501 PMCID: PMC3517519 DOI: 10.1371/journal.pone.0051439] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Accepted: 10/31/2012] [Indexed: 01/10/2023] Open
Abstract
Human respiratory syncytial virus (RSV) is an important cause of severe lower respiratory tract infections in infants and the elderly. In the vast majority of cases, however, RSV infections run mild and symptoms resemble those of a common cold. The immunological, clinical, and epidemiological profile of severe RSV infections suggests a disease caused by a virus with typical seasonal transmission behavior, lacking clear-cut virulence factors, but instead causing disease by modifying the host’s immune response in a way that stimulates pathogenesis. Yet, the interplay between RSV-evoked immune responses and epidemic behavior, and how this affects the genomic evolutionary dynamics of the virus, remains poorly understood. Here, we present a comprehensive collection of 33 novel RSV subgroup A genomes from strains sampled over the last decade, and provide the first measurement of RSV-A genomic diversity through time in a phylodynamic framework. In addition, we map amino acid substitutions per protein to determine mutational hotspots in specific domains. Using Bayesian genealogical inference, we estimated the genomic evolutionary rate to be 6.47×10−4 (credible interval: 5.56×10−4, 7.38×10−4) substitutions/site/year, considerably slower than previous estimates based on G gene sequences only. The G gene is however marked by elevated substitution rates compared to other RSV genes, which can be attributed to relaxed selective constraints. In line with this, site-specific selection analyses identify the G gene as the major target of diversifying selection. Importantly, statistical analysis demonstrates that the immune driven positive selection does not leave a measurable imprint on the genome phylogeny, implying that RSV lineage replacement mainly follows nonselective epidemiological processes. The roughly 50 years of RSV-A genomic evolution are characterized by a constant population size through time and general co-circulation of lineages over many epidemic seasons – a conclusion that might be taken into account when developing future therapeutic and preventive strategies.
Collapse
|
|
40
|
Diversity and adaptation of human respiratory syncytial virus genotypes circulating in two distinct communities: public hospital and day care center. Viruses 2012. [PMID: 23202489 PMCID: PMC3509657 DOI: 10.3390/v4112432] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
HRSV is one of the most important pathogens causing acute respiratory tract diseases as bronchiolitis and pneumonia among infants. HRSV was isolated from two distinct communities, a public day care center and a public hospital in São José do Rio Preto - SP, Brazil. We obtained partial sequences from G gene that were used on phylogenetic and selection pressure analysis. HRSV accounted for 29% of respiratory infections in hospitalized children and 7.7% in day care center children. On phylogenetic analysis of 60 HRSV strains, 48 (80%) clustered within or adjacent to the GA1 genotype; GA5, NA1, NA2, BA-IV and SAB1 were also observed. SJRP GA1 strains presented variations among deduced amino acids composition and lost the potential O-glycosilation site at amino acid position 295, nevertheless this resulted in an insertion of two potential O-glycosilation sites at positions 296 and 297. Furthermore, a potential O-glycosilation site insertion, at position 293, was only observed for hospital strains. Using SLAC and MEME methods, only amino acid 274 was identified to be under positive selection. This is the first report on HRSV circulation and genotypes classification derived from a day care center community in Brazil.
Collapse
|
|
41
|
Suzuki A, Lupisan S, Furuse Y, Fuji N, Saito M, Tamaki R, Galang H, Sombrero L, Mondoy M, Aniceto R, Olveda R, Oshitani H. Respiratory viruses from hospitalized children with severe pneumonia in the Philippines. BMC Infect Dis 2012; 12:267. [PMID: 23092190 PMCID: PMC3519714 DOI: 10.1186/1471-2334-12-267] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Accepted: 10/18/2012] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Pneumonia remains a leading cause of child death in developing countries. The viruses in severe pneumonia remain poorly defined. METHODS The study was conducted at the Eastern Visayas Regional Medical Center in Tacloban City, Philippines from May 2008 to May 2009. Patients aged 8 days to 13 years old who were admitted to the Department of Pediatrics with severe pneumonia were enrolled for the study. Upon admission, polymerase chain reaction was performed using nasopharyngeal swabs and blood cultures to detect respiratory viruses and bacteria, respectively. RESULT Among the 819 patients enrolled, at least one virus was detected in 501 cases (61.2%). In addition, 423 cases were positive for a single virus while bacteria were detected in the blood culture sample of 31 cases. The most commonly detected viruses were human rhinoviruses (n = 189), including types A (n = 103), B (n = 17), and C (n = 69), and respiratory syncytial virus (RSV) (n = 165). Novel viruses such as human metapneumovirus, human coronavirus NL63, human bocavirus, and human polyomaviruses WU and KI were also detected. There were 70 deaths, and one or more viruses were detected in 35 (50%) of these cases. Positivity only for influenza A virus (OR = 4.3, 95% CI = 1.3-14.6) was significantly associated with fatal outcome. From the blood culture, Burkholderia cepacia group (n = 9), Streptococcus pneumoniae (n = 4), Staphylococcus aureus (n = 4), Haemophilus influenzae (n = 1), and Salmonella C1 (n = 1) were also isolated. CONCLUSION Viruses were commonly detected in children with severe pneumonia in the Philippines. Hence, viral etiologies should be considered while developing better effective strategies to reduce child pneumonia-related deaths in developing countries.
Collapse
Affiliation(s)
- Akira Suzuki
- Department of Virology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
42
|
Katzov-Eckert H, Botosso VF, Neto EA, Zanotto PMDA, and the VGND consortium. Phylodynamics and dispersal of HRSV entails its permanence in the general population in between yearly outbreaks in children. PLoS One 2012; 7:e41953. [PMID: 23077477 PMCID: PMC3471929 DOI: 10.1371/journal.pone.0041953] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Accepted: 06/29/2012] [Indexed: 12/22/2022] Open
Abstract
Background Human respiratory syncytial virus (HRSV) is one of the major etiologic agents of respiratory tract infections among children worldwide. Methodology/Principal Findings Here through a comprehensive analysis of the two major HRSV groups A and B (n = 1983) which comprise of several genotypes, we present a complex pattern of population dynamics of HRSV over a time period of 50 years (1956–2006). Circulation pattern of HRSV revealed a series of expansions and fluctuations of co-circulating lineages with a predominance of HRSVA. Positively selected amino acid substitutions of the G glycoprotein occurred upon population growth of GB3 with a 60-nucleotide insertion (GB3 Insert), while other genotypes acquired substitutions upon both population growth and decrease, thus possibly reflecting a role for immune selected epitopes in linkage to the traced substitution sites that may have important relevance for vaccine design. Analysis evidenced the co-circulation and predominance of distinct HRSV genotypes in Brazil and suggested a year-round presence of the virus. In Brazil, GA2 and GA5 were the main culprits of HRSV outbreaks until recently, when the GB3 Insert became highly prevalent. Using Bayesian methods, we determined the dispersal patterns of genotypes through several inferred migratory routes. Conclusions/Significance Genotypes spread across continents and between neighboring areas. Crucially, genotypes also remained at any given region for extended periods, independent of seasonal outbreaks possibly maintained by re-infecting the general population.
Collapse
Affiliation(s)
- Hagit Katzov-Eckert
- Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Biomedical Sciences Institute-ICB-II, University of São Paulo, São Paulo, Brazil
| | | | - Eurico Arruda Neto
- Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil, and the VGDN Consortium
| | - Paolo Marinho de Andrade Zanotto
- Laboratory of Molecular Evolution and Bioinformatics, Department of Microbiology, Biomedical Sciences Institute-ICB-II, University of São Paulo, São Paulo, Brazil
- * E-mail:
| | | |
Collapse
|
|
43
|
Tedcastle AB, Fenwick F, Ingram RE, King BJ, Robinson MJ, Toms GL. The characterization of monoclonal antibodies to human metapneumovirus and the detection of multiple forms of the virus nucleoprotein and phosphoprotein. J Med Virol 2012; 84:1061-70. [DOI: 10.1002/jmv.23298] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
|
|
44
|
Regev L, Meningher T, Hindiyeh M, Mendelson E, Mandelboim M. Increase human metapneumovirus mediated morbidity following pandemic influenza infection. PLoS One 2012; 7:e34750. [PMID: 22496855 PMCID: PMC3319622 DOI: 10.1371/journal.pone.0034750] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2011] [Accepted: 03/08/2012] [Indexed: 01/15/2023] Open
Abstract
Human metapneumovirus (hMPV) is a recently discovered respiratory pathogen, infecting mainly young children. The infected patients suffer from influenza like symptoms (ILS). In Israel the virus is mainly circulating in February to March. Here we report on an increased rate of hMPV infection in the winter season of 2009–10. The 2009–10 infection had several unique characteristics when compared to previous seasons; it started around January and a large number of infants were infected by the virus. Genetic analysis based on the viral L and F genes of hMPV showed that only subtypes A2 and B2 circulated in Israel. Additionally, we have identified a novel variant of hMPV within subgroup A2b, which subdivide it into A2b1 and A2b2. Finally, we showed that the hMPV infection was detected in the country soon after the infection with the pandemic influenza virus had declined, that infection with the pandemic influenza virus was dominant and that it interfered with the infection of other respiratory viruses. Thus, we suggest that the unusual increase in hMPV infection observed in 2009–10 was due to the appearance of the pandemic influenza virus in the winter season prior to 2009–10.
Collapse
Affiliation(s)
- Liora Regev
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat-Gan, Israel
| | - Tal Meningher
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat-Gan, Israel
- Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
| | - Musa Hindiyeh
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat-Gan, Israel
| | - Ella Mendelson
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat-Gan, Israel
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Michal Mandelboim
- Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Center, Ramat-Gan, Israel
- * E-mail:
| |
Collapse
|
|
45
|
Yoshida A, Kiyota N, Kobayashi M, Nishimura K, Tsutsui R, Tsukagoshi H, Hirano E, Yamamoto N, Ryo A, Saitoh M, Harada S, Inoue O, Kozawa K, Tanaka R, Noda M, Okabe N, Tashiro M, Mizuta K, Kimura H. Molecular epidemiology of the attachment glycoprotein (G) gene in respiratory syncytial virus in children with acute respiratory infection in Japan in 2009/2010. J Med Microbiol 2012; 61:820-829. [PMID: 22383445 DOI: 10.1099/jmm.0.041137-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
This study performed a detailed genetic analysis of the glycoprotein (G) gene of respiratory syncytial virus (RSV) detected in 50 Japanese children with acute respiratory infection (ARI) in the 2009/2010 season. A phylogenetic tree constructed by the neighbour-joining method showed that 34 and 16 of the RSV strains could be classified into subgroups A and B, respectively. Strains belonging to subgroups A and B were further subdivided into GA2 and BA, respectively. The nucleotide and deduced amino acid sequence identities were relatively high among these strains (>90%). The deduced amino acid sequences implied that a relatively high frequency of amino acid substitutions occurred in the C-terminal 3rd hypervariable region of the G protein in these strains. In addition, some positively selected sites were estimated. The results suggest that RSV with genotypes GA2 and BA was associated with ARI in Japanese children in 2009/2010.
Collapse
Affiliation(s)
- Ayako Yoshida
- Aomori Prefectural Institute of Public Health and Environment, 1-1-1 Higashitsukurimichi, Aomori-shi, Aomori 030-8566, Japan
| | - Naoko Kiyota
- Kumamoto Prefectural Institute of Public Health and Environmental Sciences, 1240-1 Kurisaki-machi, Uto-shi, Kumamoto 869-0425, Japan
| | - Miho Kobayashi
- Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
| | - Koichi Nishimura
- Kumamoto Prefectural Institute of Public Health and Environmental Sciences, 1240-1 Kurisaki-machi, Uto-shi, Kumamoto 869-0425, Japan
| | - Rika Tsutsui
- Aomori Prefectural Institute of Public Health and Environment, 1-1-1 Higashitsukurimichi, Aomori-shi, Aomori 030-8566, Japan
| | - Hiroyuki Tsukagoshi
- Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
| | - Eiko Hirano
- Fukui Prefectural Institute of Public Health and Environmental Science, 39-4 Harame-cho, Fukui-shi, Fukui 910-8551, Japan
| | - Norio Yamamoto
- Influenza Virus Research Center and Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan
| | - Akihide Ryo
- Department of Molecular Biodefence Research, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan
| | - Mika Saitoh
- Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
| | - Seiya Harada
- Kumamoto Prefectural Institute of Public Health and Environmental Sciences, 1240-1 Kurisaki-machi, Uto-shi, Kumamoto 869-0425, Japan
| | - Osamu Inoue
- Aomori Prefectural Institute of Public Health and Environment, 1-1-1 Higashitsukurimichi, Aomori-shi, Aomori 030-8566, Japan
| | - Kunihisa Kozawa
- Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
| | - Ryota Tanaka
- Department of Surgery, Institute of Medical Sciences, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan
| | - Masahiro Noda
- Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan
| | - Nobuhiko Okabe
- Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan
| | - Masato Tashiro
- Influenza Virus Research Center and Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan
| | - Katsumi Mizuta
- Yamagata Prefectural Institute of Public Health, 1-6-6 Toka-machi, Yamagata-shi, Yamagata 990-0031, Japan
| | - Hirokazu Kimura
- Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.,Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
| |
Collapse
|
|
46
|
Different NF-κB activation characteristics of human respiratory syncytial virus subgroups A and B. Microb Pathog 2012; 52:184-91. [DOI: 10.1016/j.micpath.2011.12.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2011] [Revised: 12/22/2011] [Accepted: 12/24/2011] [Indexed: 11/21/2022]
|
|
47
|
A study of the genetic variability of human respiratory syncytial virus (HRSV) in Cambodia reveals the existence of a new HRSV group B genotype. J Clin Microbiol 2011; 49:3504-13. [PMID: 21865418 DOI: 10.1128/jcm.01131-11] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Human respiratory syncytial virus (HRSV) is the leading cause of hospitalization of children aged <5 years due to respiratory illness in industrialized countries, and pneumonia is the leading cause of mortality among children aged <5 years worldwide. Although HRSV was first identified in 1956, a preventative vaccine has yet to be developed. Here we report the results of the first study to investigate the circulation and genetic diversity of HRSV in Cambodia among an all-ages population over 5 consecutive years. The incidences of HRSV infection among all-ages outpatient and hospitalized populations were equivalent, at 9.5% and 8.2%, respectively. Infection was most prevalent among children aged <5 years, with bronchiolitis being the most frequently observed clinical syndrome in the same age group. Circulation of HRSV was seasonal, typically coinciding with the rainy season between July and November annually. Strains belonging to HRSV groups A and B were detected with equivalent frequencies; however, we observed a potentially biennial shift in the predominant circulating HRSV genotype. The majority of HRSV group B strains belonged to the recently described BA genotype, with the exception of 10 strains classified as belonging to a novel HRSV group B genotype, SAB4, first reported here.
Collapse
|