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Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry

Author

Listed:
  • Matteo Rizzato

    (Westphalian Wilhelms-University of Münster)

  • Fuxiang Mao

    (Westphalian Wilhelms-University of Münster)

  • Florian Chardon

    (Westphalian Wilhelms-University of Münster)

  • Kun-Yi Lai

    (Westphalian Wilhelms-University of Münster
    Westphalian Wilhelms-University of Münster)

  • Ruth Villalonga-Planells

    (Westphalian Wilhelms-University of Münster)

  • Hannes C. A. Drexler

    (Max Planck Institute for Molecular Biomedicine)

  • Marion E. Pesenti

    (Max Planck Institute of Molecular Physiology)

  • Mert Fiskin

    (UMR 7242 Biotechnologie et signalisation cellulaire, CNRS, UdS, ESBS)

  • Nora Roos

    (Institute of Medical Virology and Epidemiology of Viral Diseases)

  • Kelly M. King

    (University of Arizona)

  • Shuaizhi Li

    (University of Arizona)

  • Eduardo R. Gamez

    (University of Arizona
    University of Hawai’i at Manoa)

  • Lilo Greune

    (Westphalian Wilhelms-University of Münster)

  • Petra Dersch

    (Westphalian Wilhelms-University of Münster)

  • Claudia Simon

    (Institute of Medical Virology and Epidemiology of Viral Diseases)

  • Murielle Masson

    (UMR 7242 Biotechnologie et signalisation cellulaire, CNRS, UdS, ESBS)

  • Koenraad Doorslaer

    (University of Arizona
    University of Arizona)

  • Samuel K. Campos

    (University of Arizona)

  • Mario Schelhaas

    (Westphalian Wilhelms-University of Münster
    Westphalian Wilhelms-University of Münster)

Abstract

Mitosis induces cellular rearrangements like spindle formation, Golgi fragmentation, and nuclear envelope breakdown. Similar to certain retroviruses, nuclear delivery during entry of human papillomavirus (HPV) genomes is facilitated by mitosis, during which minor capsid protein L2 tethers viral DNA to mitotic chromosomes. However, the mechanism of viral genome delivery and tethering to condensed chromosomes is barely understood. It is unclear, which cellular proteins facilitate this process or how this process is regulated. This work identifies crucial phosphorylations on HPV minor capsid protein L2 occurring at mitosis onset. L2’s chromosome binding region (CBR) is sequentially phosphorylated by the master mitotic kinases CDK1 and PLK1. L2 phosphorylation, thus, regulates timely delivery of HPV vDNA to mitotic chromatin during mitosis. In summary, our work demonstrates a crucial role of mitotic kinases for nuclear delivery of viral DNA and provides important insights into the molecular mechanism of pathogen import into the nucleus during mitosis.

Suggested Citation

  • Matteo Rizzato & Fuxiang Mao & Florian Chardon & Kun-Yi Lai & Ruth Villalonga-Planells & Hannes C. A. Drexler & Marion E. Pesenti & Mert Fiskin & Nora Roos & Kelly M. King & Shuaizhi Li & Eduardo R. G, 2023. "Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-35874-w
    DOI: 10.1038/s41467-023-35874-w
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