Programa de Maestría y Doctorado en Ciencias Bioquímicas, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 Ciudad de México, Mexico; Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, San Fernando No. 22, Col. Sección XVI, Tlalpan, 14080 Ciudad de México, Mexico.
CONACyT-Instituto Nacional de Cancerología, San Fernando No. 22, Col. Sección XVI, Tlalpan, 14080 Ciudad de Mexico, Mexico.
Virus Res. 2018 Feb 15;246:35-45. doi: 10.1016/j.virusres.2018.01.003. Epub 2018 Jan 11.
High-risk Human Papillomavirus (HR-HPV) is the causative agent of different human cancers. A persistent HR-HPV infection alters several cellular processes involved in cell proliferation, apoptosis, immune evasion, genomic instability and transformation. Cumulative evidence from past studies indicates that HR-HPV proteins are associated with oxidative stress (OS) and has been proposed as a risk factor for cancer development. Reactive oxygen and nitrogen species (RONS) regulate a plethora of processes inducing cellular proliferation, differentiation and death. Oxidative stress (OS) is generated when an imbalance in the redox state occurs due to deregulation of the oxidant and antioxidant systems, which, in turn, promotes the damage of DNA, proteins and lipids, allowing the accumulation of mutations and genome instability. OS has been associated with the establishment and development of different cancers, and it has recently been proposed as a co-factor in cervical cancer development. This review is focused on evidence regarding the association of OS with HR-HPV proteins, and the interplay of the viral proteins with different elements of the antioxidant and DNA damage response (DDR) systems, emphasizing the processes that might be required for the viral life cycle and viral DNA integration into the host genome, which is a key element in the carcinogenic process induced by HR-HPV.
高危型人乳头瘤病毒（HR-HPV）是引发多种人类癌症的病原体。持续性 HR-HPV 感染会改变涉及细胞增殖、凋亡、免疫逃逸、基因组不稳定性和转化的几个细胞过程。过去研究的累积证据表明，HR-HPV 蛋白与氧化应激（OS）有关，并被认为是癌症发展的危险因素。活性氧和氮物种（RONS）调节着大量诱导细胞增殖、分化和死亡的过程。当氧化还原状态失衡导致氧化剂和抗氧化剂系统失调时，就会产生氧化应激（OS），这反过来又会促进 DNA、蛋白质和脂质的损伤，从而允许突变和基因组不稳定性的积累。OS 与不同癌症的建立和发展有关，最近有人提出，OS 是宫颈癌发展的一个共同因素。这篇综述的重点是关于 OS 与 HR-HPV 蛋白之间关联的证据，以及病毒蛋白与抗氧化和 DNA 损伤反应（DDR）系统不同元素之间的相互作用，强调了可能需要这些过程来完成病毒生命周期和病毒 DNA 整合到宿主基因组中，这是 HR-HPV 诱导致癌过程中的一个关键因素。
