Contribution of NS1 Effector Domain Dimerization to Influenza A Virus Replication and Virulence

被引：29

作者：

Ayllon, Juan ^{[1
]}

Russell, Rupert J. ^{[4
]}

Garcia-Sastre, Adolfo ^{[1
,2
,3
]}

Hale, Benjamin G. ^{[1
]}

机构：

[1] Mt Sinai Sch Med, Dept Microbiol, New York, NY USA

[2] Mt Sinai Sch Med, Dept Med, New York, NY USA

[3] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY USA

[4] Univ St Andrews, St Andrews, Fife, Scotland

来源：

JOURNAL OF VIROLOGY | 2012年 / 86卷 / 23期

基金：

美国国家卫生研究院;

关键词：

NUCLEAR EXPORT; RNA-BINDING; PROTEIN; INHIBITION; RECOGNITION; INTERFERON;

D O I：

10.1128/JVI.02237-12

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Conserved tryptophan-187 facilitates homodimerization of the influenza A virus NS1 protein effector domain. We generated a mutant influenza virus strain expressing NS1-W187R to destabilize this self-interaction. NS1-W187R protein exhibited lower double-stranded RNA (dsRNA)-binding activity, showed a temporal redistribution during infection, and was minimally compromised for interferon antagonism. The mutant virus replicated similarly to the wild type in vitro, but it was slightly attenuated for replication in mice, causing notably reduced morbidity and mortality. These data suggest biological relevance for the W187-mediated homotypic interaction of NS1.

引用

收藏

页码：13095 / 13098

页数：4

相关论文

共 24 条

[1] Dimer Interface of the Effector Domain of Non-structural Protein 1 from Influenza A Virus AN INTERFACE WITH MULTIPLE FUNCTIONS [J].

Aramini, James M. ;

Ma, Li-Chung ;

Zhou, Ligang ;

Schauder, Curtis M. ;

Hamilton, Keith ;

Amer, Brendan R. ;

Mack, Timothy R. ;

Lee, Hsiau-Wei ;

Ciccosanti, Colleen T. ;

Zhao, Li ;

Xiao, Rong ;

Krug, Robert M. ;

Montelione, Gaetano T. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (29) :26050-26060

[2] Influenza virus NS1 protein counteracts PKR-mediated inhibition of replication [J].

Bergmann, M ;

Garcia-Sastre, A ;

Carnero, E ;

Pehamberger, H ;

Wolff, K ;

Palese, P ;

Muster, T .

JOURNAL OF VIROLOGY, 2000, 74 (13) :6203-6206

[3] X-ray structure of NS1 from a highly pathogenic H5N1 influenza virus [J].

Bornholdt, Zachary A. ;

Prasad, B. V. Venkataram .

NATURE, 2008, 456 (7224) :985-U85

[4] Structural basis for dsRNA recognition by NS1 protein of influenza A virus [J].

Cheng, Ao ;

Wong, Sek Man ;

Yuan, Y. Adam .

CELL RESEARCH, 2009, 19 (02) :187-195

[5]

DeLano W.L., 2002, The PyMOL molecular graphics system

[6] Rescue of influenza A virus from recombinant DNA [J].

Fodor, E ;

Devenish, L ;

Engelhardt, OG ;

Palese, P ;

Brownlee, GG ;

García-Sastre, A .

JOURNAL OF VIROLOGY, 1999, 73 (11) :9679-9682

[7] Influenza A Virus NS1 Targets the Ubiquitin Ligase TRIM25 to Evade Recognition by the Host Viral RNA Sensor RIG-I [J].

Gack, Michaela Ulrike ;

Albrecht, Randy Allen ;

Urano, Tomohiko ;

Inn, Kyung-Soo ;

Huang, I-Chueh ;

Carnero, Elena ;

Farzan, Michael ;

Inoue, Satoshi ;

Jung, Jae Ung ;

Garcia-Sastre, Adolfo .

CELL HOST & MICROBE, 2009, 5 (05) :439-449

[8] Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems [J].

García-Sastre, A ;

Egorov, A ;

Matassov, D ;

Brandt, S ;

Levy, DE ;

Durbin, JE ;

Palese, P ;

Muster, T .

VIROLOGY, 1998, 252 (02) :324-330

[9] The multifunctional NS1 protein of influenza A viruses [J].

Hale, Benjamin G. ;

Randall, Richard E. ;

Ortin, Juan ;

Jackson, David .

JOURNAL OF GENERAL VIROLOGY, 2008, 89 :2359-2376

[10] Structure of an avian influenza A virus NS1 protein effector domain [J].

Hale, Benjamin G. ;

Barclay, Wendy S. ;

Randall, Richard E. ;

Russell, Rupert J. .

VIROLOGY, 2008, 378 (01) :1-5