The Serine/Threonine Kinase AP2-Associated Kinase 1 Plays an Important Role in Rabies Virus Entry

文献类型： 外文期刊

第一作者： Wang, Chong

作者： Wang, Chong;Wang, Jinliang;Shuai, Lei;Ma, Xiao;Zhang, Hailin;Liu, Renqiang;Chen, Weiye;Wang, Xijun;Ge, Jinying;Wen, Zhiyuan;Bu, Zhigao;Bu, Zhigao

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关键词： rabies; AAK1; sunitinib

期刊名称：VIRUSES-BASEL （ 影响因子：5.048； 五年影响因子：5.127 ）

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年卷期： 2020 年 12 卷 1 期

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收录情况： SCI

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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