Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology

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dc.contributor.authorTan, Lydiaen_ZA
dc.contributor.authorLemey, Philippeen_ZA
dc.contributor.authorHouspie, Lieseloten_ZA
dc.contributor.authorViveen, Marco Cen_ZA
dc.contributor.authorJansen, Nicolaas J Gen_ZA
dc.contributor.authorLoon, Anton M vanen_ZA
dc.contributor.authorWiertz, Emmanuelen_ZA
dc.contributor.authorBleek, Grada M vanen_ZA
dc.contributor.authorMartin, Darren Pen_ZA
dc.contributor.authorCoenjaerts, Frank Een_ZA
dc.date.accessioned2016-01-11T06:53:28Z
dc.date.available2016-01-11T06:53:28Z
dc.date.issued2012en_ZA
dc.description.abstractHuman 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.en_ZA
dc.identifier.apacitationTan, L., Lemey, P., Houspie, L., Viveen, M. C., Jansen, N. J. G., Loon, A. M. v., ... Coenjaerts, F. E. (2012). Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology. <i>PLoS One</i>, http://hdl.handle.net/11427/16278en_ZA
dc.identifier.chicagocitationTan, Lydia, Philippe Lemey, Lieselot Houspie, Marco C Viveen, Nicolaas J G Jansen, Anton M van Loon, Emmanuel Wiertz, Grada M van Bleek, Darren P Martin, and Frank E Coenjaerts "Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology." <i>PLoS One</i> (2012) http://hdl.handle.net/11427/16278en_ZA
dc.identifier.citationTan, L., Lemey, P., Houspie, L., Viveen, M. C., Jansen, N. J. G., van Loon, A. M., ... & Coenjaerts, F. E. J. (2012). Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology. PLoS ONE, 7(12), e51439-1. doi:10.1371/journal.pone.0051439en_ZA
dc.identifier.ris TY - Journal Article AU - Tan, Lydia AU - Lemey, Philippe AU - Houspie, Lieselot AU - Viveen, Marco C AU - Jansen, Nicolaas J G AU - Loon, Anton M van AU - Wiertz, Emmanuel AU - Bleek, Grada M van AU - Martin, Darren P AU - Coenjaerts, Frank E AB - 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. DA - 2012 DB - OpenUCT DO - 10.1371/journal.pone.0051439 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2012 T1 - Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology TI - Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology UR - http://hdl.handle.net/11427/16278 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16278
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0051439
dc.identifier.vancouvercitationTan L, Lemey P, Houspie L, Viveen MC, Jansen NJG, Loon AMv, et al. Genetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiology. PLoS One. 2012; http://hdl.handle.net/11427/16278.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2012 Tan et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherGenome evolutionen_ZA
dc.subject.otherPlant genomicsen_ZA
dc.subject.otherPhylogenetic analysisen_ZA
dc.subject.otherEvolutionary geneticsen_ZA
dc.subject.otherSequence alignmenten_ZA
dc.subject.otherViral evolutionen_ZA
dc.subject.otherPhylogeneticsen_ZA
dc.subject.otherEvolutionary immunologyen_ZA
dc.titleGenetic variability among complete human respiratory syncytial virus subgroup A genomes: bridging molecular evolutionary dynamics and epidemiologyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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