TY - JOUR
T1 - Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry
AU - Rizzato, Matteo
AU - Mao, Fuxiang
AU - Chardon, Florian
AU - Lai, Kun Yi
AU - Villalonga-Planells, Ruth
AU - Drexler, Hannes C.A.
AU - Pesenti, Marion E.
AU - Fiskin, Mert
AU - Roos, Nora
AU - King, Kelly M.
AU - Li, Shuaizhi
AU - Gamez, Eduardo R.
AU - Greune, Lilo
AU - Dersch, Petra
AU - Simon, Claudia
AU - Masson, Murielle
AU - Van Doorslaer, Koenraad
AU - Campos, Samuel K.
AU - Schelhaas, Mario
N1 - Funding Information:
We thank D. Kaiser and I. Fels for technical support, and members of the Schelhaas laboratory for critical comments on the manuscript. We thank Dr. Martin Müller for the K4 antibody. This study was supported by the European Research Council (ERC consolidator grant 682899 MitoVIn to M.S.), by the European Research Agency (Infect-ERA grant HPV-MOTIVA to M.M. and M.S.), and by the German Research Foundation (DFG, grant SCHE 1552/6-1 to M.S.). The funders had no role in study design, data collection, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85146550989&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85146550989&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-35874-w
DO - 10.1038/s41467-023-35874-w
M3 - Article
C2 - 36683055
AN - SCOPUS:85146550989
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 355
ER -