HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells

Nat Immunol. 2008 Mar;9(3):301-9. doi: 10.1038/ni1566. Epub 2008 Feb 10.


Infection with human immunodeficiency virus 1 (HIV-1) results in the dissemination of virus to gut-associated lymphoid tissue. Subsequently, HIV-1 mediates massive depletion of gut CD4+ T cells, which contributes to HIV-1-induced immune dysfunction. The migration of lymphocytes to gut-associated lymphoid tissue is mediated by integrin alpha4beta7. We demonstrate here that the HIV-1 envelope protein gp120 bound to an activated form of alpha4beta7. This interaction was mediated by a tripeptide in the V2 loop of gp120, a peptide motif that mimics structures presented by the natural ligands of alpha4beta7. On CD4+ T cells, engagement of alpha4beta7 by gp120 resulted in rapid activation of LFA-1, the central integrin involved in the establishment of virological synapses, which facilitate efficient cell-to-cell spreading of HIV-1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Cell Movement / immunology
  • Cells, Cultured
  • Fibroblasts / metabolism
  • Fibroblasts / virology
  • Flow Cytometry
  • HIV Envelope Protein gp120 / metabolism*
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Integrins / metabolism*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / virology
  • Killer Cells, Natural / immunology
  • Ligands
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Protein Binding / immunology
  • Signal Transduction / immunology


  • HIV Envelope Protein gp120
  • Integrins
  • Ligands
  • Lymphocyte Function-Associated Antigen-1
  • integrin alpha4beta7