Institute of Cellular Virology, Westphalian Wilhelms-University of Münster, Münster, Germany.
Interfaculty Centre 'Cells in Motion' (CiM), Westphalian Wilhelms-University of Münster, Münster, Germany.
Nat Commun. 2023 Jan 23;14(1):355. doi: 10.1038/s41467-023-35874-w.
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.
有丝分裂会引起细胞重排，如纺锤体形成、高尔基体碎片化和核膜破裂。类似于某些逆转录病毒，人类乳头瘤病毒（HPV）基因组进入时的核内传递是由有丝分裂介导的，在此过程中，次要衣壳蛋白 L2 将病毒 DNA 连接到有丝分裂染色体上。然而，病毒基因组传递和与浓缩染色体的连接的机制还知之甚少。目前尚不清楚哪些细胞蛋白有助于这一过程，也不清楚这一过程是如何被调控的。本研究鉴定了 HPV 次要衣壳蛋白 L2 在有丝分裂起始时发生的关键磷酸化。主有丝分裂激酶 CDK1 和 PLK1 依次对 L2 的染色体结合区（CBR）进行磷酸化。因此，L2 的磷酸化调节了 HPV vDNA 在有丝分裂期间向有丝分裂染色质的适时传递。总之，我们的工作证明了有丝分裂激酶在病毒 DNA 的核内传递中的关键作用，并为有丝分裂期间病原体进入细胞核的分子机制提供了重要的见解。
