Blocking HIV-1 infection via CCR5 and CXCR4 receptors by acting in trans on the CCR2 chemokine receptor

EMBO J. 2004 Jan 14;23(1):66-76. doi: 10.1038/sj.emboj.7600020. Epub 2003 Dec 11.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / metabolism
  • Blotting, Western
  • Calcium / metabolism
  • Cell Line
  • Chemokine CCL2 / pharmacology
  • Chemokines, CC / metabolism
  • Chemotaxis
  • Culture Media, Serum-Free
  • Dimerization
  • Down-Regulation
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Genes, Reporter
  • HIV Infections / metabolism
  • HIV Infections / prevention & control*
  • HIV-1 / immunology*
  • HIV-1 / metabolism*
  • Humans
  • Isoleucine / metabolism
  • Kinetics
  • Ligands
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Precipitin Tests
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / immunology
  • Receptors, CCR5 / metabolism*
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / immunology
  • Receptors, CXCR4 / metabolism*
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antibodies, Monoclonal
  • Chemokine CCL2
  • Chemokines, CC
  • Culture Media, Serum-Free
  • Ligands
  • Receptors, CCR5
  • Receptors, CXCR4
  • Receptors, Chemokine
  • Isoleucine
  • Calcium