全基因组 CRISPR-Cas9 筛选鉴定 CYTH2 宿主基因为流感病毒感染的潜在治疗靶点。
Genome-wide CRISPR-Cas9 screening identifies the CYTH2 host gene as a potential therapeutic target of influenza viral infection.
机构信息
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.
Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200000, China.
出版信息
Cell Rep. 2022 Mar 29;38(13):110559. doi: 10.1016/j.celrep.2022.110559.
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.
宿主基因是病毒感染的关键，由于其针对不同病毒亚型的普遍特征和最小化耐药性，因此成为极具潜力的抗病毒药物靶点。有鉴于此，我们进行了一轮又一轮的生存选择的全基因组 CRISPR-Cas9 筛选。在该筛选中富集了几个宿主唾液酸生物合成和运输的关键基因，包括细胞溶质素 2（CYTH2）、四肽重复蛋白 24（TTC24）和 N-乙酰神经氨酸合酶（NANS），我们证实这些基因负责有效的流感病毒感染。此外，我们揭示了 CYTH2 通过介导内体运输在流感病毒感染的早期阶段是必需的。此外，CYTH2 拮抗剂 SecinH3 可减轻体内流感病毒感染。总之，这些数据表明，CYTH2 是开发针对流感病毒感染的宿主导向抗病毒药物和治疗方法的有吸引力的靶点。
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