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Vesicle-associated membrane protein 5 is an intrinsic defense factor for embryonic stem cells against coronaviruses

文献类型： 外文期刊

作者： Dong, Huijun 1 ; Pan, Zihang 1 ; Jiao, Pengtao 3 ; Ye, Fei 5 ; Peng, Qi 4 ; Yu, Yanying 6 ; Lai, Xinyuan 1 ; Li, Huan 1 ; Guan, Zhao 1 ; Deng, Juan 1 ; Shen, Tao 1 ; Tan, Wenjie 5 ; Shi, Yi 4 ; Ding, Qiang 6 ; Luo, Jianyuan 7 ; Li, Tong 1 ; Zhuang, Hui 1 ; Xiang, Kuanhui 1 ;

作者机构： 1.Peking Univ, Sch Basic Med Sci, Dept Microbiol, Hlth Sci Ctr, Beijing 100191, Peoples R China

2.Peking Univ, Infect Dis Ctr, Hlth Sci Ctr, Sch Basic Med Sci, Beijing 100191, Peoples R China

3.Chinese Acad Agr Sci, Inst Anim Sci, Beijing 100193, Peoples R China

4.Chinese Acad Sci, CAS Key Lab Pathogen Microbiol & Immunol, Inst Microbiol, Beijing 100101, Peoples R China

5.China CDC, Natl Inst Viral Dis Control & Prevent, Beijing 102206, Peoples R China

6.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China

7.Peking Univ, Hlth Sci Ctr, Ctr Med Genet, Sch Basic Med Sci,Dept Med Genet, Beijing, Peoples R China

期刊名称：NATURE COMMUNICATIONS （ 影响因子：15.7； 五年影响因子：17.2 ）

ISSN：

年卷期： 2025 年 16 卷 1 期

页码：

收录情况： SCI

摘要： Embryonic stem cells (ESCs) display a distinctive resistance against various viruses, irrespective of any interferon response. Nevertheless, the underlying mechanism of this resistance remains unclear. In this study, we identify vesicle-associated membrane protein 5 (VAMP5) as a potent cell-autonomous defense factor against coronaviruses, including SARS-CoV-2, with high expression levels observed in ESCs and mesoderm. VAMP5 not only exhibits functional conservation in restricting the replication of SARS-CoV-2 and its variants, as well as other highly pathogenic coronaviruses, but also shows efficacy in combating the replication of viruses from other families. Mechanistic investigations reveal that VAMP5 localizes to double membrane vesicles (DMVs) and impedes viral replication by relying on its vesicle-side C-terminal domain to interact with the viral non-structural protein 8 (NSP8), thus inhibiting the synthesis of negative-strand RNA. Our research demonstrates that VAMP5 in ESCs disrupts the protected environment of DMVs, which is essential for viral genome replication, and interacts with RNA replication complexes to defend against viral infection. This provides a novel strategy for developing broad-spectrum antiviral treatments.

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