Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA, USA.
Cell Cycle. 2010 Sep 15;9(18):3715-22. doi: 10.4161/cc.9.18.12930. Epub 2010 Sep 7.
Infection with HIV-1 induces a variety of biological alterations to the host that are beneficial to the life cycle of the virus but may have adverse effects on the host cell. Here we demonstrate that expression of Rad51, a major component of the homologous recombination-directed DNA repair (HRR) pathway, is induced upon HIV-1 infection of microglial cells. Activation of Rad51 expression positively impacts on HIV-1 LTR transcription through a region of the viral promoter known for binding the inducible transcription factor NFκB. Rad51 showed the ability to form a complex with the p65 subunit of NFκB and regulate the level of p65 interaction with LTR DNA encompassing the κB motif. This study provides evidence for reciprocal interaction of HIV-1 and a host DNA repair protein that impacts on expression of the viral genome. These results also point to the ability of HIV-1 to recruit proteins involved in DNA repair that are necessary for retroviral DNA integration, efficient replication and prevention of viral-induced cell death.
HIV-1 感染会引起宿主的多种生物学改变，这些改变有利于病毒的生命周期，但可能对宿主细胞产生不利影响。在这里，我们证明了 Rad51 的表达在 HIV-1 感染小胶质细胞后被诱导。Rad51 表达的激活通过病毒启动子中已知与诱导转录因子 NFκB 结合的区域，对 HIV-1 LTR 转录产生积极影响。Rad51 显示出与 NFκB 的 p65 亚基形成复合物的能力，并调节 p65 与包含 κB 基序的 LTR DNA 的相互作用水平。这项研究为 HIV-1 和宿主 DNA 修复蛋白的相互作用提供了证据，这种相互作用影响病毒基因组的表达。这些结果还表明，HIV-1 能够招募参与 DNA 修复的蛋白质，这些蛋白质是逆转录病毒 DNA 整合、有效复制和防止病毒诱导的细胞死亡所必需的。
