An essential role for LEDGF/p75 in HIV integration

Manuel Llano, Dyana T. Saenz, Anne Meehan, Phonphimon Wongthida, Mary Peretz, William H. Walker, Wulin Teo, Eric M. Poeschla

Research output: Contribution to journalArticle

383 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)461-464
Number of pages4
JournalScience
Volume314
Issue number5798
DOIs
StatePublished - Oct 20 2006

ASJC Scopus subject areas

  • General

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    Llano, M., Saenz, D. T., Meehan, A., Wongthida, P., Peretz, M., Walker, W. H., Teo, W., & Poeschla, E. M. (2006). An essential role for LEDGF/p75 in HIV integration. Science, 314(5798), 461-464. https://doi.org/10.1126/science.1132319