Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry.
Fiche publication
Date publication
janvier 2023
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MASSON Murielle
Tous les auteurs :
Rizzato M, Mao F, Chardon F, Lai KY, Villalonga-Planells R, Drexler HCA, Pesenti ME, Fiskin M, Roos N, King KM, Li S, Gamez ER, Greune L, Dersch P, Simon C, Masson M, Van Doorslaer K, Campos SK, Schelhaas M
Lien Pubmed
Résumé
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.
Mots clés
Humans, Capsid Proteins, metabolism, DNA, Viral, genetics, Papillomavirus Infections, Virus Internalization, Mitosis, Phosphorylation, Genome, Viral, Cell Cycle Proteins, metabolism
Référence
Nat Commun. 2023 01 23;14(1):355