Contribution of host nucleoporin 62 in HIV-1 integrase chromatin association and viral DNA integration

J Biol Chem. 2012 Mar 23;287(13):10544-10555. doi: 10.1074/jbc.M111.317057. Epub 2012 Feb 3.

Abstract

HIV-1 integration is promoted by viral integrase (IN) and its cellular cofactors. The lens epithelium-derived growth factor (LEDGF/p75), an IN interacting cellular cofactor, has been shown to play an important role in HIV-1 chromatin targeting and integration. However, whether other cellular cofactors are also involved in viral replication steps is still elusive. Here, we show that nucleoporin 62 (Nup62) is a chromatin-bound protein and can specifically interact with HIV-1 IN in both soluble nuclear extract and chromatin-bound fractions. The knockdown of Nup62 by shRNA reduced the association of IN with host chromatin and significantly impaired viral integration and replication in HIV-1-susceptible cells. Furthermore, the expression of the IN-binding region of Nup62 in CD4(+) T cells significantly inhibited HIV-1 infection. Taken together, these results indicate that the cellular Nup62 is specifically recruited by HIV-1 IN and contribute to an efficient viral DNA integration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / virology
  • DNA, Viral / genetics
  • DNA, Viral / metabolism*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • HIV Infections / genetics
  • HIV Infections / metabolism*
  • HIV Integrase / genetics
  • HIV Integrase / metabolism*
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Virus Integration / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA, Viral
  • Membrane Glycoproteins
  • Nuclear Pore Complex Proteins
  • PSIP1 protein, human
  • Transcription Factors
  • nuclear pore protein p62
  • HIV Integrase