Parsing the role of NSP1 in SARS-CoV-2 infection

被引：44

作者：

Fisher, Tal ^{[1
]}

Gluck, Avi

Narayanan, Krishna ^{[2
]}

Kuroda, Makoto ^{[3
]}

Nachshon, Aharon ^{[1
]}

Hsu, Jason C. ^{[2
]}

Halfmann, Peter J. ^{[3
]}

Yahalom-Ronen, Yfat ^{[4
]}

Tamir, Hadas ^{[4
]}

Finkel, Yaara ^{[1
]}

Schwartz, Michal ^{[1
]}

Weiss, Shay ^{[4
]}

Tseng, Chien-Te K. ^{[2
,5
]}

Israely, Tomer ^{[4
]}

Paran, Nir ^{[4
]}

Kawaoka, Yoshihiro ^{[3
,6
,7
]}

Makino, Shinji ^{[2
,5
]}

Stern-Ginossar, Noam ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel

[2] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

[3] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53711 USA

[4] Israel Inst Biol Res, Dept Infect Dis, IL-74100 Ness Ziona, Israel

[5] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA

[6] Univ Tokyo, Inst Med Sci, Dept Virol, Tokyo 1088639, Japan

[7] Natl Ctr Global Hlth & Med Res Inst, Res Ctr Global Viral Dis, Tokyo 1628655, Japan

来源：

CELL REPORTS | 2022年 / 39卷 / 11期

基金：

美国国家卫生研究院;

关键词：

SYNDROME CORONAVIRUS INFECTION; HOST PROTEIN-SYNTHESIS; GENE-EXPRESSION; NONSTRUCTURAL PROTEIN-1; PATHOGENICITY FACTOR; RNA; INTERFERON; TRANSLATION;

D O I：

10.1016/j.celrep.2022.110954

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to shutoff of protein synthesis, and nsp1, a central shutoff factor in coronaviruses, inhibits cellular mRNA translation. However, the diverse molecular mechanisms employed by nsp1 as well as its functional importance are unresolved. By overexpressing various nsp1 mutants and generating a SARS-CoV-2 mutant, we show that nsp1, through inhibition of translation and induction of mRNA degradation, targets translated cellular mRNA and is the main driver of host shutoff during infection. The propagation of nsp1 mutant virus is inhibited exclusively in cells with intact interferon (IFN) pathway as well as in vivo, in hamsters, and this attenuation is associated with stronger induction of type I IFN response. Therefore, although nsp1???s shutoff activity is broad, it plays an essential role, specifically in counteracting the IFN response. Overall, our results reveal the multifaceted approach nsp1 uses to shut off cellular protein synthesis and uncover nsp1???s explicit role in blocking the IFN response.

引用

页数：25

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