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

Drew Weissman (), Ronald L. Rabin, James Arthos, Andrea Rubbert, Mark Dybul, Ruth Swofford, Sundararajan Venkatesan, Joshua M. Farber and Anthony S. Fauci
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Drew Weissman: University of Pennsylvania Medical Center
James Arthos: Laboratory of Immunoregulation, Laboratory of Clinical Investigation, Flow Cytometry Unit, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Andrea Rubbert: Laboratory of Immunoregulation, Laboratory of Clinical Investigation, Flow Cytometry Unit, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Mark Dybul: Laboratory of Immunoregulation, Laboratory of Clinical Investigation, Flow Cytometry Unit, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Ruth Swofford: Laboratory of Immunoregulation, Laboratory of Clinical Investigation, Flow Cytometry Unit, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Sundararajan Venkatesan: Laboratory of Immunoregulation, Laboratory of Clinical Investigation, Flow Cytometry Unit, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Joshua M. Farber: Laboratory of Immunoregulation, Laboratory of Clinical Investigation, Flow Cytometry Unit, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Anthony S. Fauci: Laboratory of Immunoregulation, Laboratory of Clinical Investigation, Flow Cytometry Unit, and Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Nature, 1997, vol. 389, issue 6654, 981-985

Abstract: 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 (reviewed in refs 1,2,3). 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 (refs 1,2,3) receptors. HIV-mediated signal transduction through CCR5 is not required for efficient fusion and entry of HIV in vitro4,5. 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 replication1,2. HIV-mediated signalling through CCR5 may also enhance viral replication invivo by increasing the activation state of target cells. Alternatively, envelope-mediated CCR5 signal transduction may influence viral-associated cytopathicity or apoptosis.

Date: 1997
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DOI: 10.1038/40173

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