PARP12 suppresses Zika virus infection through PARP-dependent degradation of NS1 and NS3 viral proteins

被引：90

作者：

Li, Lili ^{[1
,2
]}

Zhao, Hui ^{[3
]}

Liu, Ping ^{[1
]}

Li, Chunfeng ^{[4
,5
,6
]}

Quanquin, Natalie ^{[7
]}

Ji, Xue ^{[3
]}

Sun, Nina ^{[1
,2
]}

Du, Peishuang ^{[1
]}

Qin, Cheng-Feng ^{[3
]}

Lu, Ning ^{[1
]}

Cheng, Genhong ^{[4
,5
,6
,7
]}

机构：

[1] Chinese Acad Sci, Inst Biophys, CAS Key Lab Infect & Immun, Beijing 100101, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100101, Peoples R China

[3] Beijing Inst Microbiol & Epidemiol, Dept Virol, State Key Lab Pathogen & Biosecur, Beijing 10071, Peoples R China

[4] Chinese Acad Med Sci, Inst Basic Med Sci, Ctr Syst Med, Beijing 100005, Peoples R China

[5] Peking Union Med Coll, Beijing 100005, Peoples R China

[6] Suzhou Inst Syst Med, Suzhou 215123, Jiangsu, Peoples R China

[7] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

来源：

SCIENCE SIGNALING | 2018年 / 11卷 / 535期

基金：

中国国家自然科学基金;

关键词：

POLY(ADP-RIBOSE) POLYMERASE; DNA-REPAIR; GENE; IDENTIFICATION; TRANSLATION; INHIBITORS; EXOSOME; DOMAIN; NS2A; ZAP;

D O I：

10.1126/scisignal.aas9332

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Zika virus infection stimulates a type I interferon (IFN) response in host cells, which suppresses viral replication. Type I IFNs exert antiviral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). To screen for antiviral ISGs that restricted Zika virus replication, we individually knocked out 21 ISGs in A549 lung cancer cells and identified PARP12 as a strong inhibitor of Zika virus replication. Our findings suggest that PARP12 mediated the ADP-ribosylation of NS1 and NS3, nonstructural viral proteins that are involved in viral replication and modulating host defense responses. This modification of NS1 and NS3 triggered their proteasome-mediated degradation. These data increase our understanding of the antiviral activity of PARP12 and suggest a molecular basis for the potential development of therapeutics against Zika virus.

引用

页数：9

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