Peer-Reviewed Journal Details
Mandatory Fields
Jagger, BW,Wise, HM,Kash, JC,Walters, KA,Wills, NM,Xiao, YL,Dunfee, RL,Schwartzman, LM,Ozinsky, A,Bell, GL,Dalton, RM,Lo, A,Efstathiou, S,Atkins, JF,Firth, AE,Taubenberger, JK,Digard, P
2012
January
Science (New York, N.Y.)
An Overlapping Protein-Coding Region in Influenza A Virus Segment 3 Modulates the Host Response
Validated
()
Optional Fields
PA SUBUNIT CELL-DEATH RNA ENDONUCLEASE DEGRADATION SUPPRESSION INFECTION SIGNALS BINDING SYSTEM
337
199
204
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.
DOI 10.1126/science.1222213
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