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Science. 2012 Jul 13;337(6091):199-204. doi: 10.1126/science.1222213. Epub 2012 Jun 28.

An overlapping protein-coding region in influenza A virus segment 3 modulates the host response.

Author information

1
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.

Abstract

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 frameshift 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.

PMID:
22745253
PMCID:
PMC3552242
DOI:
10.1126/science.1222213
[Indexed for MEDLINE]
Free PMC Article

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