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An Overlapping Protein-Coding Region in Influenza A Virus Segment 3 Modulates the Host Response

Research output: Contribution to journalArticle

  • B. W. Jagger
  • H. M. Wise
  • J. C. Kash
  • K. A. Walters
  • N. M. Wills
  • Y. L. Xiao
  • R. L. Dunfee
  • L. M. Schwartzman
  • A. Ozinsky
  • G. L. Bell
  • R. M. Dalton
  • A. Lo
  • S. Efstathiou
  • J. F. Atkins
  • A. E. Firth
  • J. K. Taubenberger
  • P. Digard

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Original languageEnglish
Pages (from-to)199-204
Number of pages6
Issue number6091
Publication statusPublished - Jul 2012


Influenza A virus (IAV) infection leads to variable and imperfectly understood pathogenicity. We report that segment 3 of the virus contains a second open reading frame ("X-ORF"), accessed via ribosomal frameshifting. The FS product, termed PA-X, comprises the endonuclease domain of the viral PA protein with a C-terminal domain encoded by the X-ORF and functions to repress cellular gene expression. PA-X also modulates IAV virulence in a mouse infection model, acting to decrease pathogenicity. Loss of PA-X expression leads to changes in the kinetics of the global host response, which notably includes increases in inflammatory, apoptotic, and T-lymphocyte signaling pathways. Thus, we have identified a previously unknown IAV protein that modulates the host response to infection, a finding with important implications for understanding IAV pathogenesis.

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