Integration of HIV-1 DNA is regulated by interplay between viral rev and cellular LEDGF/p75 proteins

Mol Med. Jan-Feb 2010;16(1-2):34-44. doi: 10.2119/molmed.2009.00133. Epub 2009 Oct 29.

Abstract

The present work describes a novel interaction between the human immunodeficiency virus type 1 (HIV-1) Rev protein and the cellular lens epithelium-derived growth factor p75 (LEDGF/p75) protein in vitro and in virus-infected cells. Here we show, for the first time, that formation of an Rev-LEDGF/p75 complex is a crucial step in regulating viral cDNA integration. Coimmunoprecipitation experiments at various times after virus infection revealed that, first, an integrase enzyme (IN)-LEDGF/p75 complex is formed, which is then replaced by a Rev-LEDGF/p75 and Rev-IN complexes. This was supported by in vitro experiments showing that Rev promotes dissociation of the IN-LEDGF/p75 complex. Combination of the viral IN and the cellular LEDGF/p75 is required for proper integration of the viral cDNA into the host chromosomal DNA. Our findings demonstrate that integration of HIV-1 cDNA is regulated by an interplay between viral Rev and the host-cell LEDGF/p75 proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • DNA, Viral / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • HIV Integrase / genetics
  • HIV Integrase / metabolism
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Interaction Domains and Motifs
  • Virus Integration / physiology*
  • rev Gene Products, Human Immunodeficiency Virus / genetics
  • rev Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • DNA, Viral
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • lens epithelium-derived growth factor
  • rev Gene Products, Human Immunodeficiency Virus
  • rev protein, Human Immunodeficiency Virus-1
  • HIV Integrase