Genome-wide CRISPR-Cas9 screening identifies the CYTH2 host gene as a potential therapeutic target of influenza viral infection

被引：20

作者：

Yi, Chenyang ^{[1
,2
]}

Cai, Cong ^{[1
,2
]}

Cheng, Ze ^{[1
,2
]}

Zhao, Yifan ^{[1
,2
]}

Yang, Xu ^{[1
,2
]}

Wu, Yue ^{[1
,2
]}

Wang, Xiaoping ^{[1
,2
]}

Jin, Zehua ^{[1
,2
]}

Xiang, Yaozu ^{[3
]}

Jin, Meilin ^{[2
,4
]}

Han, Li ^{[1
]}

Zhang, Anding ^{[1
,2
,4
]}

机构：

[1] Huazhong Agr Univ, Coll Vet Med, State Key Lab Agr Microbiol, Hubei Hongshan Lab, Wuhan 430070, Hubei, Peoples R China

[2] Cooperat Innovat Ctr Sustainable Pig Prod, Key Lab Prevent Vet Med Hubei Prov, Wuhan 430070, Hubei, Peoples R China

[3] Tongji Univ, Shanghai East Hosp, Sch Life Sci & Technol, Shanghai 200000, Peoples R China

[4] Minist Agr Peoples Republ China, Key Lab Dev Vet Diagnost Prod, Wuhan 430070, Hubei, Peoples R China

来源：

CELL REPORTS | 2022年 / 38卷 / 13期

关键词：

NUCLEOTIDE EXCHANGE FACTOR; WEST-NILE-VIRUS; LOW-PH; CONFORMATIONAL-CHANGE; G-PROTEINS; A H1N1; ARF6; RNA; ACTIVATION; BINDING;

D O I：

10.1016/j.celrep.2022.110559

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Host genes critical for viral infection are effective antiviral drug targets with tremendous potential due to their universal characteristics against different subtypes of viruses and minimization of drug resistance. Accordingly, we execute a genome-wide CRISPR-Cas9 screen with multiple rounds of survival selection. Enriched in this screen are several genes critical for host sialic acid biosynthesis and transportation, including the cytohesin 2 (CYTH2), tetratricopeptide repeat protein 24 (TTC24), and N-acetylneuraminate synthase (NANS), which we confirm are responsible for efficient influenza viral infection. Moreover, we reveal that CYTH2 is required for the early stage of influenza virus infection by mediating endosomal trafficking. Furthermore, CYTH2 antagonist SecinH3 blunts influenza virus infection in vivo. In summary, these data suggest that CYTH2 is an attractive target for developing host-directed antiviral drugs and therapeutics against influenza virus infection.

引用

页数：24

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