An essential role for LEDGF/p75 in HIV integration
An essential role for LEDGF/p75 in HIV integration
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DOI：
10.1126/science.1132319
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发表时间：
2006-10-20
期刊：
影响因子：
56.9
通讯作者：
Poeschla, Eric M.
中科院分区：
文献类型：
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作者：
Llano, Manuel;Saenz, Dyana T.;Poeschla, Eric M.
染色体整合使人类免疫缺陷病毒（HIV）能够建立一个永久的库，可以通过治疗抑制，但不能根除。细胞蛋白在这一专性复制步骤中的参与尚不清楚。我们使用强化RNA干扰和显性阴性蛋白方法来证明细胞转录辅激活因子晶状体上皮衍生生长因子(LEDGF)/p75 （p75）是一种重要的HIV整合辅因子。该机制需要p75在整合酶和染色质之间形成的分子链的两种连接。微小水平的内源性p75足以实现整合，这表明在进入后与HIV结合的细胞因子可能在较低强度的敲除中无法被识别。干扰p75-整合酶相互作用可能具有治疗潜力。
Chromosomal integration enables human immunodeficiency virus (HIV) to establish a permanent reservoir that can be therapeutically suppressed but not eradicated. Participation of cellular proteins in this obligate replication step is poorly understood. We used intensified RNA interference and dominant-negative protein approaches to show that the cellular transcriptional coactivator lens epithelium - derived growth factor (LEDGF)/p75 (p75) is an essential HIV integration cofactor. The mechanism requires both linkages of a molecular tether that p75 forms between integrase and chromatin. Fractionally minute levels of endogenous p75 are sufficient to enable integration, showing that cellular factors that engage HIV after entry may elude identification in less intensive knockdowns. Perturbing the p75-integrase interaction may have therapeutic potential.