DNA damage response is hijacked by human papillomaviruses to complete their life cycle

Abstract

The DNA damage response (DDR) is activated when DNA is altered by intrinsic or extrinsic agents. This pathway is a complex signaling network and plays important roles in genome stability, tumor transformation, and cell cycle regulation. Human papillomaviruses (HPVs) are the main etiological agents of cervical cancer. Cervical cancer ranks as the fourth most common cancer among women and the second most frequent cause of cancer-related death worldwide. Over 200 types of HPVs have been identified and about one third of these infect the genital tract. The HPV life cycle is associated with epithelial differentiation. Recent studies have shown that HPVs deregulate the DDR to achieve a productive life cycle. In this review, I summarize current findings about how HPVs mediate the ataxia-telangiectasia mutated kinase (ATM) and the ATM- and RAD3-related kinase (ATR) DDRs, and focus on the roles that ATM and ATR signalings play in HPV viral replication. In addition, I demonstrate that the signal transducer and activator of transcription-5 (STAT)-5, an important immune regulator, can promote ATM and ATR activations through different mechanisms. These findings may provide novel opportunities for development of new therapeutic targets for HPV-related cancers.

概要

本文总结目前学术界对人类乳突病毒如何利用DNA 损伤修复来完成其复制的认识。DNA 损伤修复对人类乳突病毒复制有不可或缺的作用。乳突病毒通过对许多DNA 损伤因子的调控来控制病毒本身的复制。值得注意的是,病毒通过磷酸化STAT-5 转录因子激活ATM和ATR DNA 损伤修复通路,这意味着在乳突病毒复制的过程中,病毒利用对免疫反应的调节来激活DNA 损伤修复机制,从而达到其复制的目的。