IFITM3 inhibits severe fever with thrombocytopenia syndrome virus entry and interacts with viral Gc protein

文献类型： 外文期刊

第一作者： Du, Shouwen

作者： Du, Shouwen;Liu, Quan;Liao, Ming;Du, Shouwen;Zhou, Boping;Wang, Jigang;Wang, Yuhang;Wang, Jiamin;Ma, Yidan;Xu, Wang;Shi, Xiaoshuang;Li, Letian;Hao, Pengfei;Jin, Ningyi;Li, Chang;Wong, Yin K.;Wang, Jigang;Hu, Lifen;Liu, Wei

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关键词： antiviral activity; Gc subunit; interferon-induced transmembrane protein 3; SFTSV; virus-IFITM3 interaction

期刊名称：JOURNAL OF MEDICAL VIROLOGY （ 影响因子：6.8； 五年影响因子：6.6 ）

ISSN： 0146-6615

年卷期： 2024 年 96 卷 3 期

页码：

收录情况： SCI

摘要： Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever disease with high fatality rate of 10%-20%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) is a broad-spectrum antiviral factor targeting viral entry. However, the antiviral activity of hIFITM3 against SFTS virus (SFTSV) and the functional mechanism of IFITM3 remains unclear. Here we demonstrate that endogenous IFITM3 provides protection against SFTSV infection and participates in the anti-SFTSV effect of type I and III interferons (IFNs). IFITM3 overexpression exhibits anti-SFTSV function by blocking Gn/Gc-mediated viral entry and fusion. Further studies showed that IFITM3 binds SFTSV Gc directly and its intramembrane domain (IMD) is responsible for this interaction and restriction of SFTSV entry. Mutation of two neighboring cysteines on IMD weakens IFITM3-Gc interaction and attenuates the antiviral activity of IFITM3, suggesting that IFITM3-Gc interaction may partly mediate the inhibition of SFTSV entry. Overall, our data demonstrate for the first time that hIFITM3 plays a critical role in the IFNs-mediated anti-SFTSV response, and uncover a novel mechanism of IFITM3 restriction of SFTSV infection, highlighting the potential of clinical intervention on SFTS disease.

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