An essential role for LEDGF/p75 in HIV integration

被引：405

作者：

Llano, Manuel ^{[1
]}

Saenz, Dyana T. ^{[1
]}

Meehan, Anne ^{[1
]}

Wongthida, Phonphimon ^{[1
]}

Peretz, Mary ^{[1
]}

Walker, William H. ^{[1
]}

Teo, Wulin ^{[1
]}

Poeschla, Eric M. ^{[1
]}

机构：

[1] Mayo Clin, Coll Med, Program Mol Med, Rochester, MN 55905 USA

来源：

SCIENCE | 2006年 / 314卷 / 5798期

关键词：

D O I：

10.1126/science.1132319

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：461 / 464

页数：4

共 15 条

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