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

Chenyang Yi; Cong Cai; Ze Cheng; Yifan Zhao; Xu Yang; Yue Wu; Xiaoping Wang; Zehua Jin; Yaozu Xiang; Meilin Jin; Li Han; Anding Zhang

doi:10.1016/j.celrep.2022.110559

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

Cell Rep. 2022 Mar 29;38(13):110559. doi: 10.1016/j.celrep.2022.110559.

Authors

Chenyang Yi¹, Cong Cai¹, Ze Cheng¹, Yifan Zhao¹, Xu Yang¹, Yue Wu¹, Xiaoping Wang¹, Zehua Jin¹, Yaozu Xiang², Meilin Jin³, Li Han⁴, Anding Zhang⁵

Affiliations

¹ State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei 430070, China.
² Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200000, China.
³ Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei 430070, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, Hubei 430070, China.
⁴ State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
⁵ State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei 430070, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People's Republic of China, Wuhan, Hubei 430070, China. Electronic address: andye8019@mail.hzau.edu.cn.

PMID: 35354039
DOI: 10.1016/j.celrep.2022.110559

Abstract

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.

Keywords: CP: Microbiology; CYTH2; SecinH3; endocytosis; genome-wide screening; influenza virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
CRISPR-Cas Systems / genetics
Endosomes
Humans
Influenza A virus* / genetics
Influenza, Human* / drug therapy
Influenza, Human* / genetics

Substances

Antiviral Agents