Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor

Nature. 1997 Oct 30;389(6654):981-5. doi: 10.1038/40173.


Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) enter target cells by forming a complex between the viral envelope protein and two cell-surface membrane receptors: CD4 and a 7-span transmembrane chemokine receptor. Isolates of HIV that differ in cellular tropism use different subsets of chemokine receptors as entry cofactors: macrophage-tropic HIVs primarily use CCR5, whereas T-cell-tropic and dual-tropic isolates use CXCR4 receptors. HIV-mediated signal transduction through CCR5 is not required for efficient fusion and entry of HIV in vitro. Here we show that recombinant envelope proteins from macrophage-tropic HIV and SIV induce a signal through CCR5 on CD4+ T cells and that envelope-mediated signal transduction through CCR5 induces chemotaxis of T cells. This chemotactic response may contribute to the pathogenesis of HIV in vivo by chemo-attracting activated CD4+ cells to sites of viral replication. HIV-mediated signalling through CCR5 may also enhance viral replication in vivo by increasing the activation state of target cells. Alternatively, envelope-mediated CCR5 signal transduction may influence viral-associated cytopathicity or apoptosis.

MeSH terms

  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • Calcium / metabolism
  • Cell Line
  • Chemokine CCL4
  • Chemotaxis
  • Gene Products, env / metabolism*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp160 / metabolism
  • HIV-1 / physiology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Macrophage Inflammatory Proteins / metabolism
  • Macrophages / metabolism
  • Macrophages / virology*
  • Membrane Glycoproteins*
  • Receptors, CCR5 / metabolism*
  • Recombinant Proteins / metabolism
  • Signal Transduction*
  • Simian Immunodeficiency Virus / physiology*
  • Viral Envelope Proteins*


  • CD4 Antigens
  • Chemokine CCL4
  • Gene Products, env
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp160
  • Macrophage Inflammatory Proteins
  • Membrane Glycoproteins
  • Receptors, CCR5
  • Recombinant Proteins
  • Viral Envelope Proteins
  • gp120 protein, Simian immunodeficiency virus
  • Calcium