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The pathogenicity and multi-organ proteomic profiles of Mpox virus infection in SIVmac239-infected rhesus macaques

Author

Listed:
  • Dong Zhang

    (Peking Union Medical College)

  • Jiangfeng Liu

    (School of Basic Medicine Peking Union Medical College)

  • Lin Zhu

    (Peking Union Medical College)

  • Baoying Huang

    (Chinese Center for Disease Control and Prevention)

  • Zhe Cong

    (Peking Union Medical College)

  • Na Li

    (Peking Union Medical College)

  • Jingjing Zhang

    (Peking Union Medical College)

  • Ting Chen

    (Peking Union Medical College)

  • Jianrong Ma

    (Peking Union Medical College)

  • Jiahan Lu

    (Peking Union Medical College)

  • Yongzhi Hou

    (Peking Union Medical College)

  • Chenbo Yang

    (Peking Union Medical College)

  • Wanjun Peng

    (School of Basic Medicine Peking Union Medical College)

  • Qiang Wei

    (Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Wenjie Tan

    (Chinese Center for Disease Control and Prevention)

  • Juntao Yang

    (School of Basic Medicine Peking Union Medical College)

  • Jing Xue

    (Peking Union Medical College
    Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

Mpox poses a heightened risk of severe disease and mortality among individuals with HIV, yet the molecular mechanisms and immunopathology underlying multi-organ damage caused by the mpox virus (MPXV), particularly in the context of HIV co-infection, remain poorly understood. Here, we observe increased MPXV replication, more extensive skin lesions, and impaired humoral and cellular immune responses in SIV-MPXV co-infected rhesus macaques compared to those infected with MPXV alone. Multi-organ proteomic and phosphoproteomic analyses reveals upregulation of proteins involved in immune and inflammatory pathways in skin lesions and across multiple organs, especially in immune-related tissues. Abnormal activation of DNA replication and cell cycle signaling pathways, which may contribute to enhanced viral replication, is evident in both MPXV and SIV-MPXV co-infected groups. CDK4/6 may present a potential therapeutic target to suppress MPXV replication. These comprehensive proteomic datasets offer valuable insights into the pathogenesis of MPXV in the context of SIV co-infection and support ongoing efforts to mitigate the impact of mpox.

Suggested Citation

  • Dong Zhang & Jiangfeng Liu & Lin Zhu & Baoying Huang & Zhe Cong & Na Li & Jingjing Zhang & Ting Chen & Jianrong Ma & Jiahan Lu & Yongzhi Hou & Chenbo Yang & Wanjun Peng & Qiang Wei & Wenjie Tan & Junt, 2025. "The pathogenicity and multi-organ proteomic profiles of Mpox virus infection in SIVmac239-infected rhesus macaques," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62919-z
    DOI: 10.1038/s41467-025-62919-z
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    References listed on IDEAS

    as
    1. Ning Zhang & Li Tang & Songgang Li & Lu Liu & Mengjuan Gao & Sisheng Wang & Daiying Chen & Yichao Zhao & Ruiqing Zheng & Armin Soleymaniniya & Lingran Zhang & Wenkang Wang & Xia Yang & Yan Ren & Congw, 2025. "Integration of multi-omics data accelerates molecular analysis of common wheat traits," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    2. Sara Reardon, 2024. "Mpox is spreading rapidly. Here are the questions researchers are racing to answer," Nature, Nature, vol. 633(8028), pages 16-17, September.
    3. Pietro Scaturro & Alexey Stukalov & Darya A. Haas & Mirko Cortese & Kalina Draganova & Anna Płaszczyca & Ralf Bartenschlager & Magdalena Götz & Andreas Pichlmair, 2018. "An orthogonal proteomic survey uncovers novel Zika virus host factors," Nature, Nature, vol. 561(7722), pages 253-257, September.
    4. Yiqi Huang & Valter Bergant & Vincent Grass & Quirin Emslander & M. Sabri Hamad & Philipp Hubel & Julia Mergner & Antonio Piras & Karsten Krey & Alexander Henrici & Rupert Öllinger & Yonas M. Tesfamar, 2024. "Multi-omics characterization of the monkeypox virus infection," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
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