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

371 Citations (Scopus)

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

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Virus Integration
Integrases
HIV
Virus Internalization
RNA Interference
Chromatin
Proteins
lens epithelium-derived growth factor
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Llano, M., Saenz, D. T., Meehan, A., Wongthida, P., Peretz, M., Walker, W. H., ... 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

An essential role for LEDGF/p75 in HIV integration. / Llano, Manuel; Saenz, Dyana T.; Meehan, Anne; Wongthida, Phonphimon; Peretz, Mary; Walker, William H.; Teo, Wulin; Poeschla, Eric M.

In: Science, Vol. 314, No. 5798, 20.10.2006, p. 461-464.

Research output: Contribution to journalArticle

Llano, M, Saenz, DT, Meehan, A, Wongthida, P, Peretz, M, Walker, WH, Teo, W & Poeschla, EM 2006, 'An essential role for LEDGF/p75 in HIV integration', Science, vol. 314, no. 5798, pp. 461-464. https://doi.org/10.1126/science.1132319
Llano M, Saenz DT, Meehan A, Wongthida P, Peretz M, Walker WH et al. An essential role for LEDGF/p75 in HIV integration. Science. 2006 Oct 20;314(5798):461-464. https://doi.org/10.1126/science.1132319
Llano, Manuel ; Saenz, Dyana T. ; Meehan, Anne ; Wongthida, Phonphimon ; Peretz, Mary ; Walker, William H. ; Teo, Wulin ; Poeschla, Eric M. / An essential role for LEDGF/p75 in HIV integration. In: Science. 2006 ; Vol. 314, No. 5798. pp. 461-464.
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