Roles for E1-independent replication and E6-mediated p53 degradation during low-risk and high-risk human papillomavirus genome maintenance

• DOI: 10.1371/journal.ppat.1007755
• Publication Date: 2019-05-13T17:32:35Z
• Authors: Isao Murakami; Nagayasu Egawa; Heather Griffin; Wen Yin; Christian Kranjec; Tomomi Nakahara; Tohru Kiyono; John Doorbar
• Keywords: Pre-replication complex

Human papillomaviruses (HPV) have genotype-specific disease associations, with high-risk alpha types causing at least 5% of all human cancers. Despite these conspicuous differences, our data show that high- and low- risk HPV use similar approaches for genome maintenance persistence. During the phase, viral episomes host cell are replicated synchronously, both low-risk types, E1 helicase is non-essential. virus amplification, replication switches from an E1-independent to E1-dependent mode, which can uncouple DNA cell. It appears E2 protein, but not E6 E7, required synchronous maintenance-replication high types. Interestingly, ability protein mediate proteosomal degradation p53 inhibit keratinocyte differentiation, was also seen E6, in this case regulated by density level gene expression. This allows support while limiting extent E6-mediated proliferation during maintenance. Both E7s could facilitate cycle re-entry differentiating cells replication. well-established differences pathogenesis cancer risk, it fundamentally molecular strategies maintain their genomes, albeit important regulatory control. Our results provide new insights into regulation persistence epithelial basal parabasal layers. Understanding minimum requirement will development therapeutic clearance.