Molecular Virology, Immunology, and Medical Genetics, Human Cancer Genetics, The Ohio State University Medical Center, The Ohio State University, Columbus, Ohio, United States of America.
PLoS One. 2011 Mar 23;6(3):e17862. doi: 10.1371/journal.pone.0017862.
An siRNA screen has identified several proteins throughout the base excision repair (BER) pathway of oxidative DNA damage as important for efficient HIV infection. The proteins identified included early repair factors such as the base damage recognition glycosylases OGG1 and MYH and the late repair factor POLß, implicating the entire BER pathway. Murine cells with deletions of the genes Ogg1, Myh, Neil1 and Polß recapitulate the defect of HIV infection in the absence of BER. Defective infection in the absence of BER proteins was also seen with the lentivirus FIV, but not the gammaretrovirus MMLV. BER proteins do not affect HIV infection through its accessory genes nor the central polypurine tract. HIV reverse transcription and nuclear entry appear unaffected by the absence of BER proteins. However, HIV integration to the host chromosome is reduced in the absence of BER proteins. Pre-integration complexes from BER deficient cell lines show reduced integration activity in vitro. Integration activity is restored by addition of recombinant BER protein POLß. Lentiviral infection and integration efficiency appears to depend on the presence of BER proteins.
一项 siRNA 筛选已经鉴定出几种在碱基切除修复（BER）途径中对氧化 DNA 损伤的蛋白质，这些蛋白质对于高效的 HIV 感染很重要。鉴定出的蛋白质包括早期修复因子，如碱基损伤识别糖苷酶 OGG1 和 MYH，以及晚期修复因子 POLβ，这表明整个 BER 途径都参与其中。缺失 Ogg1、Myh、Neil1 和 Polβ 基因的小鼠细胞重现了没有 BER 时 HIV 感染的缺陷。在没有 BER 蛋白的情况下，缺乏感染性也见于慢病毒 FIV，但不是γ逆转录病毒 MMLV。BER 蛋白不会通过其辅助基因或中央多嘧啶序列影响 HIV 感染。HIV 逆转录和核进入似乎不受 BER 蛋白缺失的影响。然而，在没有 BER 蛋白的情况下，HIV 整合到宿主染色体的情况减少。来自 BER 缺陷细胞系的预整合复合物在体外显示出降低的整合活性。通过添加重组 BER 蛋白 POLβ 可以恢复整合活性。慢病毒感染和整合效率似乎取决于 BER 蛋白的存在。
