In Vivo RNAi Screening Identifies MDA5 as a Significant Contributor to the Cellular Defense against Influenza A Virus

被引：68

作者：

Benitez, Asiel A. ^{[1
]}

Panis, Maryline ^{[1
]}

Xue, Jia ^{[2
]}

Varble, Andrew ^{[1
]}

Shim, Jaehee V. ^{[1
]}

Frick, Amy L. ^{[3
]}

Lopez, Carolina B. ^{[2
]}

Sachs, David ^{[4
]}

tenOever, Benjamin R. ^{[1
]}

机构：

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

[2] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA

[3] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

来源：

CELL REPORTS | 2015年 / 11卷 / 11期

关键词：

DOUBLE-STRANDED-RNA; WEST-NILE-VIRUS; RIG-I; NS1; PROTEIN; BETA-INTERFERON; MESSENGER-RNA; V-PROTEINS; RECOGNITION; ACTIVATION; INDUCTION;

D O I：

10.1016/j.celrep.2015.05.032

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Responding to an influenza A virus (IAV) infection demands an effective intrinsic cellular defense strategy to slow replication. To identify contributing host factors to this defense, we exploited the host microRNA pathway to perform an in vivo RNAi screen. To this end, IAV, lacking a functional NS1 antagonist, was engineered to encode individual siRNAs against antiviral host genes in an effort to rescue attenuation. This screening platform resulted in the enrichment of strains targeting virus-activated transcription factors, specific antiviral effectors, and intracellular pattern recognition receptors (PRRs). Interestingly, in addition to RIG-I, the PRR for IAV, a virus with the capacity to silence MDA5 also emerged as a dominant strain in wild-type, but not in MDA5-deficient mice. Transcriptional profiling of infected knockout cells confirmed RIG-I to be the primary PRR for IAV but implicated MDA5 as a significant contributor to the cellular defense against influenza A virus.

引用

页码：1714 / 1726

页数：13

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