Strain-Specific Contribution of NS1-Activated Phosphoinositide 3-Kinase Signaling to Influenza A Virus Replication and Virulence

被引：31

作者：

Ayllon, Juan ^{[1
]}

Hale, Benjamin G. ^{[1
,4
]}

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

机构：

[1] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 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] MRC Univ Glasgow Ctr Virus Res, Glasgow, Lanark, Scotland

来源：

JOURNAL OF VIROLOGY | 2012年 / 86卷 / 09期

基金：

美国国家卫生研究院;

关键词：

NS1; PROTEIN; PHOSPHATIDYLINOSITOL-3-KINASE PI3K; ACTIVATION; PATHWAY; INFECTION; P85-BETA; BINDING; CELLS;

D O I：

10.1128/JVI.06722-11

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

We generated influenza A viruses expressing mutant NS1 proteins unable to activate phosphoinositide 3-kinase (PI3K) in two mouse-lethal strains. The recombinant A/Puerto Rico/8/34 (rPR8) mutant virus strain was attenuated and caused reduced morbidity/mortality. For the recombinant A/WSN/33 (rWSN) virus strain, the inability to stimulate PI3K had minimal impact on replication or morbidity/mortality. Cell-based assays revealed subtly distinct intracellular sites of NS1 localization and PI3K activation between the strains. We hypothesize that specific spatially regulated NS1-activated PI3K signaling, rather than simply the total level of active PI3K, is important for virus replication and virulence.

引用

页码：5366 / 5370

页数：5

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