Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Viruses. 2021 Sep 16;13(9):1846. doi: 10.3390/v13091846.
Papillomaviruses cause persistent, and usually self-limiting, infections in the mucosal and cutaneous surfaces of the host epithelium. However, in some cases, infection with an oncogenic HPV can lead to cancer. The viral genome is a small, double-stranded circular DNA molecule that is assembled into nucleosomes at all stages of infection. The viral minichromosome replicates at a low copy number in the nucleus of persistently infected cells using the cellular replication machinery. When the infected cells differentiate, the virus hijacks the host DNA damage and repair pathways to replicate viral DNA to a high copy number to generate progeny virions. This strategy is highly effective and requires a close association between viral and host chromatin, as well as cellular processes associated with DNA replication, repair, and transcription. However, this association can lead to accidental integration of the viral genome into host DNA, and under certain circumstances integration can promote oncogenesis. Here we describe the fate of viral DNA at each stage of the viral life cycle and how this might facilitate accidental integration and subsequent carcinogenesis.
乳头瘤病毒在宿主上皮的黏膜和皮肤表面引起持续的、通常是自限性的感染。然而，在某些情况下，感染致癌 HPV 可导致癌症。病毒基因组是一个小的双链环状 DNA 分子，在感染的所有阶段都被组装成核小体。病毒微染色体在持续感染细胞的核内以低拷贝数复制，利用细胞复制机制。当受感染的细胞分化时，病毒劫持宿主的 DNA 损伤和修复途径，以高拷贝数复制病毒 DNA，生成子代病毒粒子。这种策略非常有效，需要病毒和宿主染色质之间以及与 DNA 复制、修复和转录相关的细胞过程密切相关。然而，这种关联可能导致病毒基因组意外整合到宿主 DNA 中，在某些情况下，整合可促进致癌作用。在这里，我们描述了病毒 DNA 在病毒生命周期的每个阶段的命运，以及这如何促进意外整合和随后的癌变。
