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

• Published in: The EMBO journal Vol. 23; no. 1; pp. 66 - 76
• Main Authors: Rodríguez-Frade, José Miguel, del Real, Gustavo, Serrano, Antonio, Hernanz-Falcón, Patricia, Soriano, Silvia F, Vila-Coro, Antonio J, de Ana, Ana Martín, Lucas, Pilar, Prieto, Ignacio, Martínez-A, Carlos, Mellado, Mario
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 14.01.2004; Blackwell Publishing Ltd
• Subjects: AIDS; Amino Acid Substitution; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - metabolism; Blotting, Western; Calcium - metabolism; Cell Line; chemokine; Chemokine CCL2 - pharmacology; chemokine receptor; 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; 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, Chemokine - genetics; Receptors, Chemokine - metabolism; Receptors, CXCR4 - genetics; Receptors, CXCR4 - immunology; Receptors, CXCR4 - metabolism; Reverse Transcriptase Polymerase Chain Reaction
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7600020

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.