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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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a family wide rt pcr assay for detection of paramyxoviruses and application to a large scale surveillance study
PLOS ONE, 2012Co-Authors: Sander Van Boheemen, Theo M. Bestebroer, Josanne H. Verhagen, Albert D. M. E. Osterhaus, Suzan D. Pas, Sander Herfst, Ron A. M. FouchierAbstract:Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 3′ end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals.
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A Family-Wide RT-PCR Assay for Detection of Paramyxoviruses and Application to a Large-Scale Surveillance Study
2011Co-Authors: Er Van Boheemen, Theo M. Bestebroer, Josanne H. Verhagen, Albert D. M. E. Osterhaus, Suzan D. Pas, Er Herfst, Ron A. M. FouchierAbstract:Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 39 end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses
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antigenic and genetic variability of human metapneumoviruses
Emerging Infectious Diseases, 2004Co-Authors: Bernadette G Van Den Hoogen, Albert D. M. E. Osterhaus, Sander Herfst, Leo Sprong, Patricia A. Cane, Rik L. De Swart, Eduardo Forleoneto, Ron A. M. FouchierAbstract:Human metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. 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.
Roberto P. Garofalo - One of the best experts on this subject based on the ideXlab platform.
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Protective Role of Nuclear Factor Erythroid 2-Related Factor 2 Against Respiratory Syncytial Virus and Human Metapneumovirus Infections
Frontiers Media S.A., 2018Co-Authors: Teodora Ivanciuc, Elena Sbrana, Antonella Casola, Roberto P. GarofaloAbstract:The pathogenesis of respiratory syncytial virus (RSV) infections is characterized by lower airway obstruction driven at great extent by the exuberant production of inflammatory cytokines. We have previously shown that RSV infection in vitro and in vivo results in production of reactive oxygen species along with reduction in the expression of antioxidant enzymes (AOEs), which are involved in maintaining the cellular oxidant–antioxidant balance. These events were associated with the concomitant reduction in nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor that controls AOE expression. The objective of the current study was to establish the role of Nrf2 in shaping innate immune responses, clinical disease, airway inflammation, and viral replication in established experimental models of intranasal RSV and human metapneumovirus (hMPV) infections, by employing mice genetically deficient for the Nrf2 gene. Compared to control wild type (WT), mice genetically deficient in Nrf2 (Nrf2 KO) developed enhanced clinical disease, airway inflammation and pathology, and significantly greater lung viral titers following experimental infection with either RSV or hMPV. In particular, compared to control mice, RSV-infected Nrf2 KO mice lost more body weight and had increased airway obstruction at time points characterized by a remarkable increase in inflammatory cytokines and airway neutrophilia. Airway levels of AOEs and enzymes that regulate synthesis of the endogenous hydrogen sulfide (H2S) pathway, which we showed to play an important antiviral function, were also decreased in RSV-infected Nrf2 KO compared to WT. In conclusion, these results suggest that Nrf2 is a critical regulator of innate, inflammatory, and disease-associated responses in the airways of mice infected with viruses that are members of the Pneumoviridae family. Importantly, the results of this study suggest that Nrf2-dependent genes, including those controlling the cellular antioxidant and H2S-generating enzymes and cytokines can affect several aspects of the antiviral response, such as airway neutrophilia, clinical disease, airway obstruction, and viral replication
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image_1_Protective Role of Nuclear Factor Erythroid 2-Related Factor 2 Against Respiratory Syncytial Virus and Human Metapneumovirus Infections.PDF
2018Co-Authors: Teodora Ivanciuc, Elena Sbrana, Antonella Casola, Roberto P. GarofaloAbstract:The pathogenesis of respiratory syncytial virus (RSV) infections is characterized by lower airway obstruction driven at great extent by the exuberant production of inflammatory cytokines. We have previously shown that RSV infection in vitro and in vivo results in production of reactive oxygen species along with reduction in the expression of antioxidant enzymes (AOEs), which are involved in maintaining the cellular oxidant–antioxidant balance. These events were associated with the concomitant reduction in nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor that controls AOE expression. The objective of the current study was to establish the role of Nrf2 in shaping innate immune responses, clinical disease, airway inflammation, and viral replication in established experimental models of intranasal RSV and human metapneumovirus (hMPV) infections, by employing mice genetically deficient for the Nrf2 gene. Compared to control wild type (WT), mice genetically deficient in Nrf2 (Nrf2 KO) developed enhanced clinical disease, airway inflammation and pathology, and significantly greater lung viral titers following experimental infection with either RSV or hMPV. In particular, compared to control mice, RSV-infected Nrf2 KO mice lost more body weight and had increased airway obstruction at time points characterized by a remarkable increase in inflammatory cytokines and airway neutrophilia. Airway levels of AOEs and enzymes that regulate synthesis of the endogenous hydrogen sulfide (H2S) pathway, which we showed to play an important antiviral function, were also decreased in RSV-infected Nrf2 KO compared to WT. In conclusion, these results suggest that Nrf2 is a critical regulator of innate, inflammatory, and disease-associated responses in the airways of mice infected with viruses that are members of the Pneumoviridae family. Importantly, the results of this study suggest that Nrf2-dependent genes, including those controlling the cellular antioxidant and H2S-generating enzymes and cytokines can affect several aspects of the antiviral response, such as airway neutrophilia, clinical disease, airway obstruction, and viral replication.
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.
Sarah J Butcher - One of the best experts on this subject based on the ideXlab platform.
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architecture of respiratory syncytial virus revealed by electron cryotomography
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Lassi Liljeroos, Magdalena Anna Krzyzaniak, Ari Helenius, Sarah J ButcherAbstract:Human respiratory syncytial virus is a human pathogen that causes severe infection of the respiratory tract. Current information about the structure of the virus and its interaction with host cells is limited. We carried out an electron cryotomographic characterization of cell culture-grown human respiratory syncytial virus to determine the architecture of the virion. The particles ranged from 100 nm to 1,000 nm in diameter and were spherical, filamentous, or a combination of the two. The filamentous morphology correlated with the presence of a cylindrical matrix protein layer linked to the inner leaflet of the viral envelope and with local ordering of the glycoprotein spikes. Recombinant viruses with only the fusion protein in their envelope showed that these glycoproteins were predominantly in the postfusion conformation, but some were also in the prefusion form. The ribonucleocapsids were left-handed, randomly oriented, and curved inside the virions. In filamentous particles, they were often adjacent to an intermediate layer of protein assigned to M2-1 (an envelope-associated protein known to mediate association of ribonucleocapsids with the matrix protein). Our results indicate important differences in structure between the Paramyxovirinae and Pneumovirinae subfamilies within the Paramyxoviridae, and provide fresh insights into host cell exit of a serious pathogen.
Albert D. M. E. Osterhaus - 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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a family wide rt pcr assay for detection of paramyxoviruses and application to a large scale surveillance study
PLOS ONE, 2012Co-Authors: Sander Van Boheemen, Theo M. Bestebroer, Josanne H. Verhagen, Albert D. M. E. Osterhaus, Suzan D. Pas, Sander Herfst, Ron A. M. FouchierAbstract:Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 3′ end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals.
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A Family-Wide RT-PCR Assay for Detection of Paramyxoviruses and Application to a Large-Scale Surveillance Study
2011Co-Authors: Er Van Boheemen, Theo M. Bestebroer, Josanne H. Verhagen, Albert D. M. E. Osterhaus, Suzan D. Pas, Er Herfst, Ron A. M. FouchierAbstract:Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 39 end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses
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antigenic and genetic variability of human metapneumoviruses
Emerging Infectious Diseases, 2004Co-Authors: Bernadette G Van Den Hoogen, Albert D. M. E. Osterhaus, Sander Herfst, Leo Sprong, Patricia A. Cane, Rik L. De Swart, Eduardo Forleoneto, Ron A. M. FouchierAbstract:Human metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. 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.