The Serine/Threonine Kinase Ap2-Associated Kinase 1 Plays An Important Role In Rabies Virus Entry
文献类型： 外文期刊
作者： 王翀;;王金良;;帅磊;;刘任强;;陈伟业;;王喜军;;葛金英;;温志远;;步志高
作者机构：
关键词： Rabies; Aak1; Sunitinib
期刊名称： VIRUSES-BASEL
ISSN： 1999-4915
年卷期： 2020 年 12 卷 1 期
页码：
收录情况： JCR（2021版）
摘要： Rabies virus (RABV) invades the central nervous system and nearly always causes fatal disease in humans. RABV enters cells via clathrin-mediated endocytosis upon receptor binding. The detailed mechanism of this process and how it is regulated are not fully understood. Here, we carried out a high-through-put RNAi analysis and identified AP2-associated kinase 1 (AAK1), a serine/threonine kinase, as an important cellular component in regulating the entry of RABV. AAK1 knock-down greatly inhibits RABV infection of cells, and AAK1-induced phosphorylation of threonine 156 of the mu subunit of adaptor protein 2 (AP2M1) is found to be required for RABV entry. Inhibition of AAK1 kinase activity by sunitinib blocked AP2M1 phosphorylation, significantly inhibiting RABV infection and preventing RABV from entering early endosomes. In vivo studies revealed that sunitinib prolongs the survival of mice challenged with RABV street virus. Our findings indicate that AAK1 is a potential drug target for postexposure prophylaxis against rabies.
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