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

Author

Listed:
  • Huijun Dong

    (Peking University Health Science Center)

  • Zihang Pan

    (Peking University Health Science Center)

  • Pengtao Jiao

    (Chinese Academy of Agricultural Sciences
    Chinese Academy of Sciences)

  • Fei Ye

    (China CDC)

  • Qi Peng

    (Chinese Academy of Sciences)

  • Yanying Yu

    (Tsinghua University)

  • Xinyuan Lai

    (Peking University Health Science Center)

  • Huan Li

    (Peking University Health Science Center)

  • Zhao Guan

    (Peking University Health Science Center)

  • Juan Deng

    (Peking University Health Science Center)

  • Tao Shen

    (Peking University Health Science Center)

  • Wenjie Tan

    (China CDC)

  • Yi Shi

    (Chinese Academy of Sciences)

  • Qiang Ding

    (Tsinghua University)

  • Jianyuan Luo

    (Peking University Health Science Center)

  • Tong Li

    (Peking University Health Science Center)

  • Hui Zhuang

    (Peking University Health Science Center)

  • Kuanhui Xiang

    (Peking University Health Science Center)

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.

Suggested Citation

  • Huijun Dong & Zihang Pan & Pengtao Jiao & Fei Ye & Qi Peng & Yanying Yu & Xinyuan Lai & Huan Li & Zhao Guan & Juan Deng & Tao Shen & Wenjie Tan & Yi Shi & Qiang Ding & Jianyuan Luo & Tong Li & Hui Zhu, 2025. "Vesicle-associated membrane protein 5 is an intrinsic defense factor for embryonic stem cells against coronaviruses," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61655-8
    DOI: 10.1038/s41467-025-61655-8
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