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Guy Boivin - One of the best experts on this subject based on the ideXlab platform.
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the distinguishing features of human Metapneumovirus and respiratory syncytial virus
Reviews in Medical Virology, 2010Co-Authors: Jesse Papenburg, Guy BoivinAbstract:Acute respiratory tract infections (RTIs) are a leading cause of morbidity and mortality worldwide. Human Metapneumovirus (hMPV) is a member of the Metapneumovirus genus within the Pneumovirinae subfamily of the Paramyxoviridae family. Though hMPV was only discovered in 2001, a large body of work has already shown that it is the aetiologic agent of a substantial proportion of upper and lower RTIs across all age groups in both healthy and immunocompromised hosts throughout the world. RSV, also a pneumovirus, is the human pathogen most closely related to hMPV. RSV is the leading cause of pneumonia and bronchiolitis in infants and young children, but can also cause respiratory tract disease in all age groups. In this paper, we will review the salient features of the virology, epidemiology, pathogenesis, host immune responses, clinical manifestations and diagnostic modalities of hMPV, using RSV as a comparison. In addition, we will show how immunoprophylactic and therapeutic strategies studied and used in clinical practice for RSV-some with great success, and others tragic failure-have led to promising areas of research for the prevention and treatment of the significant burden of disease caused by hMPV.
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the distinguishing features of human Metapneumovirus and respiratory syncytial virus
Reviews in Medical Virology, 2010Co-Authors: Jesse Papenburg, Guy BoivinAbstract:Acute respiratory tract infections (RTIs) are a leading cause of morbidity and mortality worldwide. Human Metapneumovirus (hMPV) is a member of the Metapneumovirus genus within the Pneumovirinae subfamily of the Paramyxoviridae family. Though hMPV was only discovered in 2001, a large body of work has already shown that it is the aetiologic agent of a substantial proportion of upper and lower RTIs across all age groups in both healthy and immunocompromised hosts throughout the world. RSV, also a pneumovirus, is the human pathogen most closely related to hMPV. RSV is the leading cause of pneumonia and bronchiolitis in infants and young children, but can also cause respiratory tract disease in all age groups. In this paper, we will review the salient features of the virology, epidemiology, pathogenesis, host immune responses, clinical manifestations and diagnostic modalities of hMPV, using RSV as a comparison. In addition, we will show how immunoprophylactic and therapeutic strategies studied and used in clinical practice for RSV—some with great success, and others tragic failure—have led to promising areas of research for the prevention and treatment of the significant burden of disease caused by hMPV. Copyright © 2010 John Wiley & Sons, Ltd.
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Human Metapneumovirus, Peru.
Emerging Infectious Diseases, 2006Co-Authors: Gregory C Gray, Yacine Abed, Ana W. Capuano, Sharon F. Setterquist, James S. Neville, Mark G. Lebeck, James G Olson, Troy A. Mccarthy, José L. Sánchez, Guy BoivinAbstract:We retrospectively studied 420 pharyngeal swab specimens collected from Peruvian and Argentinean patients with influenzalike illness in 2002 and 2003 for evidence of human Metapneumovirus (HMPV). Twelve specimens (2.3%) were positive by multiple assays. Six specimens yielded HMPV isolates. Four of the 6 isolates were of the uncommon B1 genotype.
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effect of ribavirin and glucocorticoid treatment in a mouse model of human Metapneumovirus infection
Antimicrobial Agents and Chemotherapy, 2006Co-Authors: Marie-Ève Hamelin, Gregory A Prince, Guy BoivinAbstract:Human Metapneumovirus (hMPV)-infected BALB/c mice were treated with ribavirin (40 mg/kg of body weight twice a day intraperitoneally), corticosterone (0.2 mg/ml in water), or both modalities. Ribavirin significantly decreased both hMPV replication in lungs (by 5 log 10 ) and global pulmonary inflammation on day 5 postinfection, whereas glucocorticoids reduced only alveolar and interstitial inflammation, compared to controls.
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human Metapneumovirus infection in adults with community acquired pneumonia and exacerbation of chronic obstructive pulmonary disease
Clinical Infectious Diseases, 2005Co-Authors: Marie-Ève Hamelin, S Cotu, Joshua Laforge, Noel Lampron, Karl Weiss, Rodica Gilca, G Deserres, Jean Bourbeau, Guy BoivinAbstract:We tested nasopharyngeal aspirate specimens by real-time polymerase chain reaction assays and paired serum samples by enzyme-linked immunosorbent assays. Acute human Metapneumovirus infections were identified in 6 (4.1%) of 145 adult patients who presented to the emergency department for pneumonia or acute exacerbation of chronic obstructive pulmonary disease during 2 winter/spring seasons in Quebec, Canada.
John V. Williams - One of the best experts on this subject based on the ideXlab platform.
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Human Metapneumovirus - what we know now
F1000Research, 2018Co-Authors: Nazly Shafagati, John V. WilliamsAbstract:Human Metapneumovirus (HMPV) is a leading cause of acute respiratory infection, particularly in children, immunocompromised patients, and the elderly. HMPV, which is closely related to avian Metapneumovirus subtype C, has circulated for at least 65 years, and nearly every child will be infected with HMPV by the age of 5. However, immunity is incomplete, and re-infections occur throughout adult life. Symptoms are similar to those of other respiratory viral infections, ranging from mild (cough, rhinorrhea, and fever) to more severe (bronchiolitis and pneumonia). The preferred method for diagnosis is reverse transcription-polymerase chain reaction as HMPV is difficult to culture. Although there have been many advances made in the past 16 years since its discovery, there are still no US Food and Drug Administration-approved antivirals or vaccines available to treat HMPV. Both small animal and non-human primate models have been established for the study of HMPV. This review will focus on the epidemiology, transmission, and clinical manifestations in humans as well as the animal models of HMPV pathogenesis and host immune response.
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Chest radiographic features of human Metapneumovirus infection in pediatric patients.
Pediatric Radiology, 2017Co-Authors: Melissa A. Hilmes, Marie R Griffin, Kathryn M. Edwards, Yuwei Zhu, F. Daniel Dunnavant, Sudha P. Singh, Wendy Danto Ellis, Daniel C. Payne, John V. WilliamsAbstract:Background Human Metapneumovirus (HMPV) was identified in 2001 and is a common cause of acute respiratory illness in young children. The radiologic characteristics of laboratory-confirmed HMPV acute respiratory illness in young children have not been systematically assessed.
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structure of the human Metapneumovirus fusion protein with neutralizing antibody identifies a pneumovirus antigenic site
Nature Structural & Molecular Biology, 2012Co-Authors: Xiaolin Wen, Reagan G Cox, George P Leser, Robert A Lamb, Jens C. Krause, John V. WilliamsAbstract:The crystal structure of the fusion protein from human Metapneumovirus in complex with a potently neutralizing antibody reveals a novel antigenic site, which could be explored to develop vaccines against this and related paramyxoviruses.
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Structure of the human Metapneumovirus fusion protein with neutralizing antibody identifies a pneumovirus antigenic site.
2012Co-Authors: Xiaolin Wen, Reagan G Cox, James E Crowe, George P Leser, Robert A Lamb, Jens C. Krause, John V. Williams, Theodore S. JardetzkyAbstract:Human Metapneumovirus and respiratory syncytial virus cause lower respiratory tract infections. The virus fusion (F) glycoprotein promotes membrane fusion by refolding from a metastable pre-fusion to a stable post-fusion conformation. F is also a major target of the neutralizing antibody response. Here we show that a potently neutralizing anti-human Metapneumovirus antibody (DS7) binds a structurally invariant domain of F, revealing a new epitope that could be targeted in vaccine development.
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population based incidence of human Metapneumovirus infection among hospitalized children
The Journal of Infectious Diseases, 2010Co-Authors: Caroline B Hall, Geoffrey A Weinberg, Marie R Griffin, Peter G. Szilagyi, Kathryn M. Edwards, Yuwei Zhu, John V. Williams, Chiaoyin K WangAbstract:Background Human Metapneumovirus (HMPV) is a leading cause of acute respiratory illness (ARI) in children. Population-based incidence rates and comprehensive clinical characterizations of disease have not been established.
Lawrence Corey - One of the best experts on this subject based on the ideXlab platform.
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brief communication fatal human Metapneumovirus infection in stem cell transplant recipients
Annals of Internal Medicine, 2006Co-Authors: Janet A Englund, Rhoda Morrow, Garrett W Nichols, David N. Fredricks, Robert C Hackman, Jane Kuypers, Michael Boeckh, Lawrence CoreyAbstract:Background: Human Metapneumovirus (hMPV), a recently discovered respiratory virus, is associated with clinical disease in young and elderly persons. Objective: To determine the importance of hMPV in hematopoietic stem-cell transplant recipients. Design: Retrospective survey of patients with consecutive residual bronchoalveolar lavage (BAL) samples. Setting: Referral cancer center. Patients: Hematopoietic stem-cell transplant recipients who underwent BAL because of lower respiratory tract disease. Measurements: Bronchoalveolar lavage specimens were assayed by quantitative real-time polymerase chain reaction methods. Results: Human Metapneumovirus was detected in BAL specimens from 5 of 163 patients (3.0%). Persistent viral infection was noted in 3 patients with several samples, and hMPV was detected in 1 of 2 lung specimens tested. Infected patients became symptomatic within the first 40 days after transplantation. Initial symptoms included fever, cough, nasal congestion, and sore throat. Clinical findings included respiratory failure, pulmonary hemorrhage, and culture-negative septic shock. Four of 5 patients died with acute respiratory failure. Limitations: This retrospective study did not evaluate asymptomatic patients or those with mild disease. Conclusion: Human Metapneumovirus infection in the lower respiratory tract is associated with respiratory failure in immunocompromised adults who were previously considered to have "idiopathic pneumonia." The infection may result in fulminant respiratory decompensation and shock after transplantation.
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Brief communication: fatal human Metapneumovirus infection in stem-cell transplant recipients.
Annals of Internal Medicine, 2006Co-Authors: Janet A Englund, David N. Fredricks, Robert C Hackman, Jane Kuypers, Michael Boeckh, W. Garrett Nichols, Rhoda Ashley Morrow, Lawrence CoreyAbstract:Human Metapneumovirus (hMPV) usually affects children and the elderly. The authors found hMPV in bronchoalveolar lavage specimens from 5 of 163 hematopoietic stem-cell transplant recipients (3.0%) ...
Ron A. M. Fouchier - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH Antigenic and Genetic Variability of
2013Co-Authors: Human Metapneumoviruses, Bernadette G Van Den Hoogen, Albert D. M. E. Osterhaus, Er Herfst, Leo Sprong, Patricia A. Cane, Eduardo Forleo-neto, Rik L. De Swart, Ron A. M. FouchierAbstract:Human Metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxoviridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups on the basis of genetic or antigenic differences or both. For HMPV, the existence of different genetic lineages has been described on the basis of variation in a limited set of available sequences. We address the antigenic relationship between genetic lineages in virus neutralization assays. In addition, we analyzed the genetic diversity of HMPV by phylogenetic analysis of sequences obtained for part of the fusion protein (n = 84) and the complete attachment protein open reading frames (n = 35). On the basis of sequence diversity between attachment protein genes and the differences in virus neutralization titers, two HMPV serotypes were defined. Each serotype could be divided into two genetic lineages, but these did not reflect major antigenic differences. Human Metapneumovirus (HMPV) has recently been identified as a causative agent of respiratory tract illnesses in humans worldwide (1–3) and is a member of the Pneumovirinae subfamily within the Paramyxoviridae family (4). The Pneumovirinae subfamily consists of two genera: the pneumoviruses and the Metapneumoviruses. Human respiratory syncytial virus (HRSV), the major viral cause of severe respiratory tract illnesses in children, is the type species of the pneumoviruses (5). Avian pneumovirus (APV), the causative agent of respiratory tract illnesses in turkeys and chickens (6), was the sole member of the Metapneumovirus genus until the discovery of HMPV (7). For most pneumoviruses, different subgroups or subtypes have been identified. For HRSV, two subgroups have been identified on the basis of differences in nucleotide sequences, reactivity patterns with monoclonal antibodies, and in vitro neutralization assays with subgroup-specifi
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Fusion protein is the main determinant of Metapneumovirus host tropism.
Journal of General Virology, 2009Co-Authors: Miranda De Graaf, Sander Herfst, Eefje J. A. Schrauwen, Albertus D M E Osterhaus, Geert Van Amerongen, Ron A. M. FouchierAbstract:Human Metapneumovirus (HMPV) and avian Metapneumovirus subgroup C (AMPV-C) infect humans and birds, respectively. This study confirmed the difference in host range in turkey poults, and analysed the contribution of the individual Metapneumovirus genes to host range in an in vitro cell-culture model. Mammalian Vero-118 cells supported replication of both HMPV and AMPV-C in contrast to avian quail fibroblast (QT6) cells in which only AMPV-C replicated to high titres. Inoculation of Vero-118 and QT6 cells with recombinant HMPV in which genes were exchanged with those of AMPV-C revealed that the Metapneumovirus fusion (F) protein is the main determinant for host tropism. Chimeric viruses in which polymerase complex proteins were exchanged between HMPV and AMPV-C replicated less efficiently compared with HMPV in QT6 cells. Using mini-genome systems, it was shown that exchanging these polymerase proteins resulted in reduced replication and transcription efficiency in QT6 cells. Examination of infected Vero-118 and QT6 cells revealed that viruses containing the F protein of AMPV-C yielded larger syncytia compared with viruses containing the HMPV F protein. Cell-content mixing assays revealed that the F protein of AMPV-C was more fusogenic compared with the F protein of HMPV, and that the F2 region is responsible for the difference observed between AMPV-C and HMPV F-promoted fusion in QT6 and Vero-118 cells. This study provides insight into the determinants of host tropism and membrane fusion of Metapneumoviruses.
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newer respiratory virus infections human Metapneumovirus avian influenza virus and human coronaviruses
Current Opinion in Infectious Diseases, 2005Co-Authors: Ron A. M. Fouchier, Guus F. Rimmelzwaan, Thijs Kuiken, Albertus D M E OsterhausAbstract:Purpose of review Recently, several previously unrecognized respiratory viral pathogens have been identified and several influenza A virus subtypes, previously known to infect poultry and wild birds, were transmitted to humans. Here we review the recent literature on these respiratory viruses. Recent findings Human Metapneumovirus has now been detected worldwide, causing severe respiratory tract illnesses primarily in very young, elderly and immunocompromised individuals. Animal models and reverse genetic techniques were designed for human Metapneumovirus, and the first vaccine candidates have been developed. Considerable genetic and antigenic diversity was observed for human Metapneumovirus, but the implication of this diversity for vaccine development and virus epidemiology requires further study. Two previously unrecognized human coronaviruses were discovered in 2004 in The Netherlands and Hong Kong. Their clinical impact and epidemiology are largely unknown and warrant further investigation. Several influenza A virus subtypes were transmitted from birds to humans, and these viruses continue to constitute a pandemic threat. The clinical symptoms associated with these zoonotic transmissions range from mild respiratory illnesses and conjunctivitis to pneumonia and acute respiratory distress syndrome, sometimes resulting in death. More basic research into virus ecology and evolution and development of effective vaccines and antiviral strategies are required to limit the impact of influenza A virus zoonoses and the threat of an influenza pandemic. Summary Previously unknown and emerging respiratory viruses are an important threat to human health. Development of virus diagnostic tests, antiviral strategies, and vaccines for each of these pathogens is crucial to limit their impact.
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real time reverse transcriptase pcr assay for detection of human Metapneumoviruses from all known genetic lineages
Journal of Clinical Microbiology, 2004Co-Authors: Jeroen Maertzdorf, Bernadette G Van Den Hoogen, Chiaoyin K Wang, Miranda De Graaf, Albert D. M. E. Osterhaus, Jennifer B Brown, Joseph D Quinto, Marla Chu, Richard R Spaete, Ron A. M. FouchierAbstract:The discovery of human Metapneumovirus and its implications for respiratory tract disease have emphasized the need for a sensitive, specific, and rapid assay to detect this virus in a clinical setting. It recently became clear that human Metapneumovirus can be grouped into at least four genetic lineages. Previously described assays for the detection of human Metapneumovirus were developed by using limited sequence information and failed to detect viruses from all four genetic lineages with comparable sensitivities. Here we describe the development and evaluation of a real-time reverse transcriptase PCR assay that detects human Metapneumovirus from the four known genetic lineages with equal specificities and sensitivities.
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Analysis of the genomic sequence of a human Metapneumovirus.
Virology, 2002Co-Authors: Bernadette G Van Den Hoogen, Theo M. Bestebroer, Albertus D M E Osterhaus, Ron A. M. FouchierAbstract:Abstract We recently described the isolation of a novel paramyxovirus from children with respiratory tract disease in The Netherlands. Based on biological properties and limited sequence information the virus was provisionally classified as the first nonavian member of the Metapneumovirus genus and named human Metapneumovirus (hMPV). This report describes the analysis of the sequences of all hMPV open reading frames (ORFs) and intergenic sequences as well as partial sequences of the genomic termini. The overall percentage of amino acid sequence identity between APV and hMPV N, P, M, F, M2-1, M2-2, and L ORFs was 56 to 88%. Some nucleotide sequence identity was also found between the noncoding regions of the APV and hMPV genomes. Although no discernible amino acid sequence identity was found between two of the ORFs of hMPV and ORFs of other paramyxoviruses, the amino acid content, hydrophilicity profiles, and location of these ORFs in the viral genome suggest that they represent SH and G proteins. The high percentage of sequence identity between APV and hMPV, their similar genomic organization (3′-N-P-M-F-M2-SH-G-L-5′), and phylogenetic analyses provide evidence for the proposed classification of hMPV as the first mammalian Metapneumovirus.
James E Crowe - One of the best experts on this subject based on the ideXlab platform.
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Structure of the human Metapneumovirus fusion protein with neutralizing antibody identifies a pneumovirus antigenic site.
2012Co-Authors: Xiaolin Wen, Reagan G Cox, James E Crowe, George P Leser, Robert A Lamb, Jens C. Krause, John V. Williams, Theodore S. JardetzkyAbstract:Human Metapneumovirus and respiratory syncytial virus cause lower respiratory tract infections. The virus fusion (F) glycoprotein promotes membrane fusion by refolding from a metastable pre-fusion to a stable post-fusion conformation. F is also a major target of the neutralizing antibody response. Here we show that a potently neutralizing anti-human Metapneumovirus antibody (DS7) binds a structurally invariant domain of F, revealing a new epitope that could be targeted in vaccine development.
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Structure of the human Metapneumovirus fusion protein with neutralizing antibody identifies a pneumovirus antigenic site. Nat Struct Mol Biol 19
2012Co-Authors: Xiaolin Wen, Reagan G Cox, James E Crowe, George P Leser, Robert A Lamb, Jens C. Krause, John Williams, Theodore S. JardetzkyAbstract:Human Metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause lower respiratory infections. The virus fusion (F) glycoprotein promotes membrane fusion by refolding from a metastable pre-fusion to a stable post-fusion conformation. F is also a major target of the neutralizing antibody response. Here we show that a potently neutralizing anti-HMPV antibody (DS7) binds a structurally invariant domain of F, identifying a new epitope that could be targeted in vaccine development. Human Metapneumovirus (HMPV) and respiratory syncytial virus (RSV)1–3 define the Pneumovirus subfamily of the Paramyxoviridae and are major respiratory pathogens, causing significant morbidity in infants and the elderly4,5. Vaccine development for HMPV and RSV has been challenging, with no licensed vaccine for either. The paramyxovirus F protein is a class I viral fusion protein and a major target of the neutralizing antibody response6. F initially folds to a metastable, pre-fusion conformation6,7 that, upon activation, undergoes large-scale refolding6–8 coupled to membrane fusion. While major antigenic sites in HMPV and RSV F have been identified, our understanding of F neutralizing epitopes remains incomplete11,16,17. The anti-HMPV F DS7 Fab was identified in a human antibod
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Human Metapneumovirus as a major cause of human respiratory tract disease.
Pediatric Infectious Disease Journal, 2004Co-Authors: James E CroweAbstract:Background: Human Metapneumovirus (hMPV) is a newly identified paramyxovirus that appears to be one of the most significant and common viral infections in humans. The virus, first isolated in 2001, is a clear cause of lower respiratory tract disease in both the very young and the frail elderly. The virus causes acute wheezing in children or, less commonly, croup or pneumonia. Methods/Results: Molecular epidemiology studies have shown that field strains exhibit sufficient sequence diversity to designate 2 subgroups of circulating viruses. Small animal and nonhuman primate models of infection have been described, which will allow studies of pathogenesis and immunity. Recombinant viruses have already been generated by several groups using reverse genetics, which facilitates the study of the biology of the virus and the generation of live attenuated vaccine candidates. Conclusions: Ongoing research promises to elucidate the molecular basis for pathogenesis and immunity of human Metapneumovirus infections and to pave the way for rapid vaccine development.
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human Metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children
The New England Journal of Medicine, 2004Co-Authors: John V. Williams, Sharon J Tollefson, Lisa L Halburntrush, Joyce M Pingsterhaus, Peter F Wright, Kathryn M. Edwards, Paul A Harris, James E CroweAbstract:Background We sought to determine the role of human Metapneumovirus in lower respiratory tract illness in previously healthy infants and children. Methods We tested nasal-wash specimens, obtained over a 25-year period from otherwise healthy children presenting with acute respiratory tract illness, for human Metapneumovirus. Results A viral cause other than human Metapneumovirus was determined for 279 of 687 visits for acute lower respiratory tract illness (41 percent) by 463 children in a population of 2009 infants and children prospectively seen from 1976 to 2001. There were 408 visits for lower respiratory tract illness by 321 children for which no cause was identified. Of these 321 children, specimens from 248 were available. Forty-nine of these 248 specimens (20 percent) contained human Metapneumovirus RNA or viable virus. Thus, 20 percent of all previously virus-negative lower respiratory tract illnesses were attributable to human Metapneumovirus, which means that 12 percent of all lower respiratory ...