Department of Molecular Genetics and Microbiology, Center for Virology, Duke University Medical Center, Durham, North Carolina 27710; email:
Annu Rev Virol. 2014 Nov;1(1):605-25. doi: 10.1146/annurev-virology-031413-085548. Epub 2014 Jul 16.
Viruses must interact with their hosts in order to replicate; these interactions often provoke the evolutionarily conserved response to DNA damage, known as the DNA damage response (DDR). The DDR can be activated by incoming viral DNA, during the integration of retroviruses, or in response to the aberrant DNA structures generated upon replication of DNA viruses. Furthermore, DNA and RNA viral proteins can induce the DDR by promoting inappropriate S phase entry, by modifying cellular DDR factors directly, or by unintentionally targeting host DNA. The DDR may be antiviral, although viruses often require proximal DDR activation of repair and recombination factors to facilitate replication as well as downstream DDR signaling suppression to ensure cell survival. An unintended consequence of DDR attenuation during infection is the long-term survival and proliferation of precancerous cells. Therefore, the molecular basis for DDR activation and attenuation by viruses remains an important area of study that will likely provide key insights into how viruses have evolved with their hosts.
病毒必须与其宿主相互作用才能复制；这些相互作用常常引发进化保守的 DNA 损伤反应，即 DNA 损伤反应（DDR）。DDR 可被外来病毒 DNA 激活，在逆转录病毒整合过程中，或在复制 DNA 病毒时产生异常 DNA 结构时激活。此外，DNA 和 RNA 病毒蛋白可以通过促进不合适的 S 期进入、直接修饰细胞 DDR 因子，或无意中靶向宿主 DNA 来诱导 DDR。DDR 可能具有抗病毒作用，尽管病毒通常需要 DDR 激活修复和重组因子，以促进复制，以及下游 DDR 信号抑制，以确保细胞存活。感染过程中 DDR 减弱的一个意外后果是癌前细胞的长期存活和增殖。因此，病毒激活和减弱 DDR 的分子基础仍然是一个重要的研究领域，这可能为我们提供关键的见解，了解病毒如何与其宿主共同进化。
