2. Academic Validation
  3. Vesicle-associated membrane protein 5 is an intrinsic defense factor for embryonic stem cells against coronaviruses

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

  • Nat Commun. 2025 Jul 7;16(1):6241. doi: 10.1038/s41467-025-61655-8.
Huijun Dong # 1,  Zihang Pan # 1,  Pengtao Jiao # 2 3,  Fei Ye 4,  Qi Peng 3,  Yanying Yu 5,  Xinyuan Lai 1,  Huan Li 1,  Zhao Guan 1,  Juan Deng 1,  Tao Shen 1,  Wenjie Tan 4,  Yi Shi 3,  Qiang Ding 5,  Jianyuan Luo 6,  Tong Li 1,  Hui Zhuang 1,  Kuanhui Xiang 7
Affiliations

Affiliations

  • 1 Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • 2 Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
  • 3 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 4 National Institute for Viral Disease Control and Prevention, China CDC, Beijing, 102206, China.
  • 5 School of Medicine, Tsinghua University, Beijing, 100084, China.
  • 6 Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
  • 7 Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China. kxiang@bjmu.edu.cn.
  • # Contributed equally.
PMID: 40624080 DOI: 10.1038/s41467-025-61655-8
Abstract

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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