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

被引：494

作者：

Jagger, B. W. ^{[1
,2
]}

Wise, H. M. ^{[1
]}

Kash, J. C. ^{[2
]}

Walters, K-A ^{[3
]}

Wills, N. M. ^{[4
]}

Xiao, Y-L ^{[2
]}

Dunfee, R. L. ^{[2
]}

Schwartzman, L. M. ^{[2
]}

Ozinsky, A. ^{[3
]}

Bell, G. L. ^{[1
]}

Dalton, R. M. ^{[1
]}

Lo, A. ^{[1
]}

Efstathiou, S. ^{[1
]}

Atkins, J. F. ^{[4
,5
]}

Firth, A. E. ^{[1
]}

Taubenberger, J. K. ^{[2
]}

Digard, P. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England

[2] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA

[3] Inst Syst Biol, Seattle, WA 98109 USA

[4] Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA

[5] Univ Coll Cork, BioSci Inst, Cork, Ireland

来源：

SCIENCE | 2012年 / 337卷 / 6091期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会; 爱尔兰科学基金会; 英国惠康基金;

关键词：

ENDONUCLEASE; DEGRADATION; SUPPRESSION; SUBUNIT; BINDING; IMMUNE;

D O I：

10.1126/science.1222213

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：199 / 204

页数：7

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