Beta-chemokine inhibition of monocytotropic HIV-1 infection. Interference with a postbinding fusion step.
The beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta have potent suppressive effects on HIV-1 infection resulting from an early postbinding block in virus fusion and entry. Inhibition was observed only with monocytotropic isolates and mapped to the V3 region of the HIV-1 envelope. RANTES did not inhibit virus expression in chronically infected cells or reduce initial virus attachment to the cell membrane. Inhibitory activity required RANTES binding to the target cell but not G protein-mediated signaling or protein tyrosine kinase activity. The results are consistent with a reversible competitive mechanism of virus inhibition that prevents a V3-associated postbinding step in membrane fusion. The data support a role for a RANTES chemokine receptor as a coreceptor for monocytotropic-HIV-1.
Oravecz
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Division of Hematologic Products, Bethesda, MD 20892, USA.
Pall
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Norcross
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MA
D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000502:physiology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D046911:Macromolecular Substances; D019402:Macrophage Inflammatory Proteins; D008561:Membrane Fusion / Q000187:drug effects; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology*; D015846:Monokines / Q000494:pharmacology*; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000187:drug effects / Q000502:physiology*; D011991:Receptors, Virus / Q000187:drug effects / Q000502:physiology
D015704:CD4 Antigens; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D046911:Macromolecular Substances; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D019713:Receptors, CCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D011991:Receptors, Virus; D018819:Dipeptidyl Peptidase 4