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    Positive Selection Drives Preferred Segment Combinations during Influenza Virus Reassortment

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    Authors
    Zeldovich, Konstantin B.
    Liu, Ping
    Renzette, Nicholas
    Foll, Matthieu
    Pham, Serena T.
    Venev, Sergey V.
    Gallagher, Glen R.
    Bolon, Daniel N.
    Kurt-Jones, Evelyn A.
    Jensen, Jeffrey D.
    Caffrey, Daniel R.
    Schiffer, Celia A.
    Kowalik, Timothy F.
    Wang, Jennifer P.
    Finberg, Robert W.
    Show allShow less
    UMass Chan Affiliations
    Department of Medicine, Division of Infectious Disease and Immunology
    Department of Biochemistry and Molecular Pharmacology
    Department of Microbiology and Physiological Systems
    Program in Bioinformatics and Integrative Biology
    Document Type
    Journal Article
    Publication Date
    2015-02-23
    Keywords
    Computational Biology
    Ecology and Evolutionary Biology
    Genomics
    Immunity
    Immunology and Infectious Disease
    Immunology of Infectious Disease
    Infectious Disease
    Molecular Biology
    Virology
    
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    Link to Full Text
    http://dx.doi.org/10.1093/molbev/msv044
    Abstract
    Influenza A virus (IAV) has a segmented genome that allows for the exchange of genome segments between different strains. This reassortment accelerates evolution by breaking linkage, helping IAV cross species barriers to potentially create highly virulent strains. Challenges associated with monitoring the process of reassortment in molecular detail have limited our understanding of its evolutionary implications. We applied a novel deep sequencing approach with quantitative analysis to assess the in vitro temporal evolution of genomic reassortment in IAV. The combination of H1N1 and H3N2 strains reproducibly generated a new H1N2 strain with the hemagglutinin and nucleoprotein segments originating from H1N1 and the remaining six segments from H3N2. By deep sequencing the entire viral genome, we monitored the evolution of reassortment, quantifying the relative abundance of all IAV genome segments from the two parent strains over time and measuring the selection coefficients of the reassorting segments. Additionally, we observed several mutations coemerging with reassortment that were not found during passaging of pure parental IAV strains. Our results demonstrate how reassortment of the segmented genome can accelerate viral evolution in IAV, potentially enabled by the emergence of a small number of individual mutations. Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    Source
    Mol Biol Evol. 2015 Feb 23. pii: msv044. Link to article on publisher's site
    DOI
    10.1093/molbev/msv044
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/34970
    PubMed ID
    25713211
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1093/molbev/msv044
    Scopus Count
    Collections
    UMass Chan Faculty and Researcher Publications
    Schiffer Lab Publications
    Program in Bioinformatics and Integrative Biology Publications

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