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Journal of Virology, July 2006, p. 7275-7280, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.02470-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Modest but Reproducible Inhibition of Human Immunodeficiency Virus Type 1 Infection in Macrophages following LEDGFp75 Silencing

Steven P. Zielske{dagger} and Mario Stevenson*

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605

Received 23 November 2005/ Accepted 3 May 2006

LEDGFp75 is a cellular protein which binds human immunodeficiency virus type 1 (HIV-1) integrase with high specificity and affinity but whose function in infection has not been defined. We infected LEDGFp75-deficient primary macrophages with wild-type HIV in order to assess potential infection phenotypes which would provide clues to LEDGFp75 function. Silencing of LEDGFp75 by 70 to 80% resulted in an average of 53% reduced infection of macrophages by HIV. Analysis of infection intermediates showed that integration, but not two-long-terminal-repeat (2LTR) circles or late cDNAs, was reduced up to 74% in LEDGFp75-deficient macrophages. Therefore, LEDGFp75 has a modest involvement in HIV-1 integration in macrophages.

* Corresponding author. Mailing address: 373 Plantation St., Suite 319, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605. Phone: (508) 856-3645. Fax: (508) 856-4075. E-mail: Mario.Stevenson{at}umassmed.edu.

{dagger} Present address: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109.

Journal of Virology, July 2006, p. 7275-7280, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.02470-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Shun, M.-C., Raghavendra, N. K., Vandegraaff, N., Daigle, J. E., Hughes, S., Kellam, P., Cherepanov, P., Engelman, A. (2007). LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes Dev. 21: 1767-1778 [Abstract] [Full Text]  
  • Pandey, K. K., Sinha, S., Grandgenett, D. P. (2007). Transcriptional Coactivator LEDGF/p75 Modulates Human Immunodeficiency Virus Type 1 Integrase-Mediated Concerted Integration. J. Virol. 81: 3969-3979 [Abstract] [Full Text]  
  • Cherepanov, P. (2007). LEDGF/p75 interacts with divergent lentiviral integrases and modulates their enzymatic activity in vitro. Nucleic Acids Res 35: 113-124 [Abstract] [Full Text]  
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