siRNA screening of a targeted library of DNA repair factors in HIV infection reveals a role for base excision repair in HIV integration.
siRNA screening of a targeted library of DNA repair factors in HIV infection reveals a role for base excision repair in HIV integration.
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DOI：
10.1371/journal.pone.0017612
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发表时间：
2011-03-23
期刊：
影响因子：
3.7
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Espeseth AS;Fishel R;Hazuda D;Huang Q;Xu M;Yoder K;Zhou H
长期以来，宿主DNA修复酶一直被认为在HIV复制中发挥作用，许多不同的DNA修复因子与HIV相关。为了确定HIV感染所需的DNA修复途径，我们使用232个siRNA池进行了有针对性的siRNA筛选，以寻找与DNA修复相关的基因。将有效的siRNA池靶向的基因映射到定义明确的DNA修复途径，发现许多靶向与短斑块碱基切除修复(BER)途径相关的酶的siRNAs减少了HIV感染。对于6个靶向BER酶的siRNA池，通过表达相应的cDNA来挽救mRNA击倒的负面影响，验证了该基因在HIV复制中的重要性。此外，缺乏特定BER酶表达的小鼠胚胎成纤维细胞(MEF)减少了HIV逆转录病毒载体的转导。研究BER酶在HIV感染中的作用表明BER途径在HIV整合中的作用。
Host DNA repair enzymes have long been assumed to play a role in HIV replication, and many different DNA repair factors have been associated with HIV. In order to identify DNA repair pathways required for HIV infection, we conducted a targeted siRNA screen using 232 siRNA pools for genes associated with DNA repair. Mapping the genes targeted by effective siRNA pools to well-defined DNA repair pathways revealed that many of the siRNAs targeting enzymes associated with the short patch base excision repair (BER) pathway reduced HIV infection. For six siRNA pools targeting BER enzymes, the negative effect of mRNA knockdown was rescued by expression of the corresponding cDNA, validating the importance of the gene in HIV replication. Additionally, mouse embryo fibroblasts (MEFs) lacking expression of specific BER enzymes had decreased transduction by HIV-based retroviral vectors. Examining the role BER enzymes play in HIV infection suggests a role for the BER pathway in HIV integration.
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