Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry

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. Gamez, Lilo Greune, Petra Dersch, Claudia Simon, Murielle Masson, Koenraad Van Doorslaer, Samuel K. Campos, Mario Schelhaas

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Article number355
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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