Modulation of the DNA damage response during the life cycle of human papillomaviruses.
Modulation of the DNA damage response during the life cycle of human papillomaviruses.
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DOI：
10.1016/j.virusres.2016.11.006
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发表时间：
2017-03-02
期刊：
影响因子：
5
通讯作者：
Moody CA
中科院分区：
文献类型：
--
作者：
Anacker DC;Moody CA
人乳头瘤病毒（HPV）是最常见的性传播病毒感染。感染某些类型的HPV会造成重大的公共卫生风险，因为这些类型与多种人类癌症有关，包括宫颈癌，其他肛门生殖器恶性肿瘤和越来越多的头颈部癌症。HPV生命周期与宿主细胞分化密切相关，晚期病毒事件如结构基因表达和病毒基因组扩增发生在复层上皮的上层。DNA损伤反应（DDR）是一个复杂的蛋白质信号网络，通过检测、信号传导和修复DNA损伤来调节复制的保真度。ATM和ATR是DNA损伤检测和修复的主要调节因子。大量研究表明，ATM（共济失调毛细血管扩张突变）和ATR（共济失调毛细血管扩张和Rad3相关）途径的激活对于HPV的有效复制至关重要。本文综述了HPV如何在整个病毒生命周期中与ATM和ATR依赖的DNA损伤反应相互作用，以创造一个支持病毒复制的环境，以及这些途径的激活如何影响基因组稳定性。
Human papillomavirus (HPV) is the most common sexually transmitted viral infection. Infection with certain types of HPV pose a major public health risk as these types are associated with multiple human cancers, including cervical cancer, other anogenital malignancies and an increasing number of head and neck cancers. The HPV life cycle is closely tied to host cell differentiation with late viral events such as structural gene expression and viral genome amplification taking place in the upper layers of the stratified epithelium. The DNA damage response (DDR) is an elaborate signaling network of proteins that regulate the fidelity of replication by detecting, signaling and repairing DNA lesions. ATM and ATR are two kinases that are major regulators of DNA damage detection and repair. A multitude of studies indicate that activation of the ATM (Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia and Rad3-related) pathways are critical for HPV to productively replicate. This review outlines how HPV interfaces with the ATM- and ATR-dependent DNA damage responses throughout the viral life cycle to create an environment supportive of viral replication and how activation of these pathways could impact genomic stability.