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.

中文翻译：

---

危险关系：染色体外 HPV 基因组的长期复制


乳头瘤病毒在宿主上皮的粘膜和皮肤表面引起持续且通常是自限性的感染。然而，在某些情况下，感染致癌 HPV 可能导致癌症。病毒基因组是一种小的双链环状 DNA 分子，在感染的各个阶段都会组装成核小体。病毒微型染色体使用细胞复制机制在持续感染细胞的细胞核中以低拷贝数复制。当受感染的细胞分化时，病毒劫持宿主 DNA 损伤并修复途径，将病毒 DNA 复制到高拷贝数，从而产生子代病毒颗粒。这种策略非常有效，需要病毒和宿主染色质以及与 DNA 复制、修复和转录相关的细胞过程之间的密切关联。然而，这种关联可能导致病毒基因组意外整合到宿主 DNA 中，并且在某些情况下整合可能促进肿瘤发生。在这里，我们描述了病毒 DNA 在病毒生命周期每个阶段的命运，以及这如何促进意外整合和随后的致癌作用。