Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment packaging while enhancing viral fitness and transmissibility

Christopher B. Brooke, William L. Ince, Jiajie Wei, Jack R. Bennink, Jonathan W. Yewdell, Robert A. Lamb

Research output: Contribution to journalArticle


The influenza A virus (IAV) genome is divided into eight distinct RNA segments believed to be copackaged into virions with nearly perfect efficiency. Here, we describe a mutation in IAV nucleoprotein (NP) that enhances replication and transmission in guinea pigs while selectively reducing neuraminidase (NA) gene segment packaging into virions. We show that incomplete IAV particles lacking gene segments contribute to the propagation of the viral population through multiplicity reactivation under conditions of widespread coinfection, which we demonstrate commonly occurs in the upper respiratory tract of guinea pigs. NP also dramatically altered the functional balance of the viral glycoproteins on particles by selectively decreasing NA expression. Our findings reveal novel functions for NP in selective control of IAV gene packaging and balancing glycoprotein expression and suggest a role for incomplete gene packaging during host adaptation and transmission.

Original languageEnglish (US)
Pages (from-to)16854-16859
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number47
StatePublished - Nov 25 2014
Externally publishedYes



  • Genome packaging
  • Genome segmentation
  • Host adaptation
  • Influenza virus
  • Nucleoprotein

ASJC Scopus subject areas

  • General

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