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The CXCL8/MAPK/hnRNP-K axis enables susceptibility to infection by EV-D68, rhinovirus, and influenza virus in vitro

Author

Listed:
  • Qingran Yang

    (Jilin University
    Jilin University)

  • Haoran Guo

    (Jilin University)

  • Huili Li

    (Jilin University)

  • Zhaoxue Li

    (Jilin University)

  • Fushun Ni

    (Jilin University)

  • Zhongmei Wen

    (Jilin University)

  • Kai Liu

    (Tsinghua University)

  • Huihui Kong

    (University of Wisconsin-Madison
    the Chinese Academy of Agricultural Sciences)

  • Wei Wei

    (Jilin University
    Jilin University)

Abstract

Respiratory viruses pose an ongoing threat to human health with excessive cytokine secretion contributing to severe illness and mortality. However, the relationship between cytokine secretion and viral infection remains poorly understood. Here we elucidate the role of CXCL8 as an early response gene to EV-D68 infection. Silencing CXCL8 or its receptors, CXCR1/2, impedes EV-D68 replication in vitro. Upon recognition of CXCL8 by CXCR1/2, the MAPK pathway is activated, facilitating the translocation of nuclear hnRNP-K to the cytoplasm. This translocation increases the recognition of viral RNA by hnRNP-K in the cytoplasm, promoting the function of the 5′ untranslated region in the viral genome. Moreover, our investigations also reveal the importance of the CXCL8 signaling pathway in the replication of both influenza virus and rhinovirus. In summary, our findings hint that these viruses exploit the CXCL8/MAPK/hnRNP-K axis to enhance viral replication in respiratory cells in vitro.

Suggested Citation

  • Qingran Yang & Haoran Guo & Huili Li & Zhaoxue Li & Fushun Ni & Zhongmei Wen & Kai Liu & Huihui Kong & Wei Wei, 2025. "The CXCL8/MAPK/hnRNP-K axis enables susceptibility to infection by EV-D68, rhinovirus, and influenza virus in vitro," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57094-0
    DOI: 10.1038/s41467-025-57094-0
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    1. David E. Gordon & Gwendolyn M. Jang & Mehdi Bouhaddou & Jiewei Xu & Kirsten Obernier & Kris M. White & Matthew J. O’Meara & Veronica V. Rezelj & Jeffrey Z. Guo & Danielle L. Swaney & Tia A. Tummino & , 2020. "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing," Nature, Nature, vol. 583(7816), pages 459-468, July.
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