School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK.
Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, West Yorkshire, LS2 9JT, UK.
J Gen Virol. 2021 Mar;102(3). doi: 10.1099/jgv.0.001540. Epub 2021 Jan 11.
Persistent infection with high-risk human papillomaviruses (HR-HPVs) is the causal factor in over 99 % of cervical cancer cases, and a significant proportion of oropharyngeal and anogenital cancers. The key drivers of HPV-mediated transformation are the oncoproteins E5, E6 and E7. Together, they act to prolong cell-cycle progression, delay differentiation and inhibit apoptosis in the host keratinocyte cell in order to generate an environment permissive for viral replication. The oncoproteins also have key roles in mediating evasion of the host immune response, enabling infection to persist. Moreover, prolonged infection within the cellular environment established by the HR-HPV oncoproteins can lead to the acquisition of host genetic mutations, eventually culminating in transformation to malignancy. In this review, we outline the many ways in which the HR-HPV oncoproteins manipulate the host cellular environment, focusing on how these activities can contribute to carcinogenesis.
高危型人乳头瘤病毒（HR-HPV）的持续感染是超过 99%宫颈癌病例以及相当一部分口咽癌和肛门生殖器癌的致病因素。HPV 介导的转化的关键驱动因素是致癌蛋白 E5、E6 和 E7。它们共同作用以延长细胞周期进程、延迟宿主角质形成细胞的分化并抑制细胞凋亡，从而为病毒复制创造一个许可的环境。致癌蛋白还在介导逃避宿主免疫反应方面发挥关键作用，使感染持续存在。此外，在 HR-HPV 致癌蛋白所建立的细胞环境中持续感染可导致宿主遗传突变的获得，最终导致癌变。在这篇综述中，我们概述了 HR-HPV 致癌蛋白操纵宿主细胞环境的多种方式，重点介绍这些活动如何促进致癌作用。
