Influenza A Virus Utilizes Suboptimal Splicing to Coordinate the Timing of Infection

被引：72

作者：

Chua, Mark A. ^{[1
]}

Schmid, Sonja ^{[2
]}

Perez, Jasmine T. ^{[2
]}

Langlois, Ryan A. ^{[2
]}

tenOever, Benjamin R. ^{[1
,2
,3
]}

机构：

[1] Mt Sinai Sch Med, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA

[3] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA

来源：

CELL REPORTS | 2013年 / 3卷 / 01期

基金：

美国国家卫生研究院;

关键词：

NUCLEAR EXPORT; NS2; PROTEIN; MATRIX PROTEIN; VIRAL-RNA; REPLICATION; TRANSCRIPTION; ASSOCIATION; EXPRESSION; RESISTANCE; MUTATIONS;

D O I：

10.1016/j.celrep.2012.12.010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Influenza A virus is unique as an RNA virus in that it replicates in the nucleus and undergoes splicing. With only ten major proteins, the virus must gain nuclear access, replicate, assemble progeny virions in the cytoplasm, and then egress. In an effort to elucidate the coordination of these events, we manipulated the transcript levels from the bicistronic nonstructural segment that encodes the spliced virus product responsible for genomic nuclear export. We find that utilization of an erroneous splice site ensures the slow accumulation of the viral nuclear export protein (NEP) while generating excessive levels of an antagonist that inhibits the cellular response to infection. Modulation of this simple transcriptional event results in improperly timed export and loss of virus infection. Together, these data demonstrate that coordination of the influenza A virus life cycle is set by a "molecular timer" that operates on the inefficient splicing of a virus transcript.

引用

页码：23 / 29

页数：7

共 33 条

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