Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor.
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.
Weissman
D
D
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. dweissman@nih.gov
Rabin
R L
RL
Arthos
J
J
Rubbert
A
A
Dybul
M
M
Swofford
R
R
Venkatesan
S
S
Farber
J M
JM
Fauci
A S
AS
D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D054407:Chemokine CCL4; D002633:Chemotaxis; D015686:Gene Products, env / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000821:virology*; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014759:Viral Envelope Proteins
D015704:CD4 Antigens; D054407:Chemokine CCL4; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus; D002118:Calcium