IFITM3 restricts RABV infection through inhibiting viral entry and mTORC1-dependent autophagy

文献类型： 外文期刊

第一作者： Ma, Jiaqi

作者： Ma, Jiaqi;Tu, Zhongzhong;Zhang, Xinying;Wang, Jie;Guo, Jianxiong;Feng, Ye;Li, Chang;Tu, Changchun;Liu, Yan;Ma, Jiaqi;He, Hongbin;Wang, Hongmei;Wang, Jie;Du, Shouwen

作者机构：

关键词： IFITM3; RABV; IFN beta; Autophagy; Anti-viral effect

期刊名称：VETERINARY MICROBIOLOGY （ 影响因子：3.3； 五年影响因子：3.5 ）

ISSN： 0378-1135

年卷期： 2023 年 284 卷

页码：

收录情况： SCI

摘要： Rabies, which caused by rabies virus (RABV), is a zoonotic and life-threatening disease with 100% mortality, and there is no effective treatment thus far due to the unclear pathogenesis and less of treatment targets. Interferon-induced transmembrane protein 3 (IFITM3) has recently been identified as an important anti-viral host effector induced by type I interferon. However, the role of IFITM3 in RABV infection has not been elucidated. In this study, we demonstrated that IFITM3 is a crucial restriction factor for RABV, the viral-induced IFITM3 significantly inhibited RABV replication, while knockdown of IFITM3 had the opposite effect. We then identified that IFN beta induces the upregulation of IFITM3 in the absence or presence of RABV infection, meanwhile, IFITM3 positively regulates RABV-triggered production of IFN beta in a feedback manner. In-depth research we found that IFITM3 not only inhibits the virus absorb and entry, but also inhibits viral replication through mTORC1dependent autophagy. All these findings broaden our understanding of IFITM3 function and uncover a novel mechanism against RABV infection.

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