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

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

来源：Science, 2012, 337(6091): 199-204.

DOI：10.1126/science.1222213

• ENDONUCLEASE
• DEGRADATION
• SUPPRESSION
• SUBUNIT
• BINDING
• IMMUNE

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.

• 出版日期2012-7-13