Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; email:
Annu Rev Virol. 2023 Sep 29;10(1):325-345. doi: 10.1146/annurev-virology-111821-103452. Epub 2023 Apr 11.
High-risk human papillomaviruses (HPVs) are associated with several human cancers. HPVs are small, DNA viruses that rely on host cell machinery for viral replication. The HPV life cycle takes place in the stratified epithelium, which is composed of different cell states, including terminally differentiating cells that are no longer active in the cell cycle. HPVs have evolved mechanisms to persist and replicate in the stratified epithelium by hijacking and modulating cellular pathways, including the DNA damage response (DDR). HPVs activate and exploit DDR pathways to promote viral replication, which in turn increases the susceptibility of the host cell to genomic instability and carcinogenesis. Here, we review recent advances in our understanding of the regulation of the host cell DDR by high-risk HPVs during the viral life cycle and discuss the potential cellular consequences of modulating DDR pathways.
高危型人乳头瘤病毒（HPV）与多种人类癌症有关。HPV 是一种小型 DNA 病毒，依赖宿主细胞机制进行病毒复制。HPV 的生命周期发生在分层上皮中，该上皮由不同的细胞状态组成，包括不再处于细胞周期中的终末分化细胞。HPV 通过劫持和调节包括 DNA 损伤反应（DDR）在内的细胞途径，进化出了在分层上皮中持续存在和复制的机制。HPV 激活并利用 DDR 途径促进病毒复制，这反过来又增加了宿主细胞对基因组不稳定性和癌变的易感性。在这里，我们回顾了近年来对高危 HPV 在病毒生命周期中对宿主细胞 DDR 调节的理解的最新进展，并讨论了调节 DDR 途径的潜在细胞后果。
