title: Macrophage-tropic HIV and SIV envelope proteins induce a signal through the CCR5 chemokine receptor.
abstract: 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.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. dweissman@nih.gov
authors.forename: D
authors.initials: D
authors.lastname: Weissman
authors.forename: R L
authors.initials: RL
authors.lastname: Rabin
authors.forename: J
authors.initials: J
authors.lastname: Arthos
authors.forename: A
authors.initials: A
authors.lastname: Rubbert
authors.forename: M
authors.initials: M
authors.lastname: Dybul
authors.forename: R
authors.initials: R
authors.lastname: Swofford
authors.forename: S
authors.initials: S
authors.lastname: Venkatesan
authors.forename: J M
authors.initials: JM
authors.lastname: Farber
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: 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
chemical_list: 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