Abstract
The identification of chemokine receptors as HIV-1 coreceptors has focused research on developing strategies to prevent HIV-1 infection. We generated CCR2-01, a CCR2 receptor-specific monoclonal antibody that neither competes with the chemokine CCL2 for binding nor triggers signaling, but nonetheless blocks replication of monotropic (R5) and T-tropic (X4) HIV-1 strains. This effect is explained by the ability of CCR2-01 to induce oligomerization of CCR2 with the CCR5 or CXCR4 viral coreceptors. HIV-1 infection through CCR5 and CXCR4 receptors can thus be prevented in the absence of steric hindrance or receptor downregulation by acting in trans on a receptor that is rarely used by the virus to infect cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Antibodies, Monoclonal / biosynthesis
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Antibodies, Monoclonal / metabolism
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Blotting, Western
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Calcium / metabolism
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Cell Line
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Chemokine CCL2 / pharmacology
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Chemokines, CC / metabolism
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Chemotaxis
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Culture Media, Serum-Free
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Dimerization
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Down-Regulation
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Electrophoresis, Polyacrylamide Gel
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Flow Cytometry
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Genes, Reporter
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HIV Infections / metabolism
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HIV Infections / prevention & control*
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HIV-1 / immunology*
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HIV-1 / metabolism*
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Humans
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Isoleucine / metabolism
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Kinetics
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Ligands
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Monocytes / drug effects
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Monocytes / metabolism
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Precipitin Tests
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Receptors, CCR5 / genetics
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Receptors, CCR5 / immunology
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Receptors, CCR5 / metabolism*
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Receptors, CXCR4 / genetics
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Receptors, CXCR4 / immunology
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Receptors, CXCR4 / metabolism*
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Receptors, Chemokine / genetics
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Receptors, Chemokine / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Antibodies, Monoclonal
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Chemokine CCL2
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Chemokines, CC
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Culture Media, Serum-Free
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Ligands
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Receptors, CCR5
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Receptors, CXCR4
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Receptors, Chemokine
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Isoleucine
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Calcium