Article
- The EMBO Journal (2004) 23, 66 - 76
- doi:10.1038/sj.emboj.7600020
Published online: 11 December 2003
Subject Categories:
Blocking HIV-1 infection via CCR5 and CXCR4 receptors by acting in trans on the CCR2 chemokine receptor
José Miguel Rodríguez-Frade, Gustavo del Real, Antonio Serrano, Patricia Hernanz-Falcón, Silvia F Soriano, Antonio J Vila-Coro, Ana Martín de Ana, Pilar Lucas, Ignacio Prieto, Carlos Martínez-A and Mario Mellado
- Department of Immunology and Oncology, Centro Nacional de Biotecnología, UAM Campus de Cantoblanco, Madrid, Spain
Correspondence to:
Mario Mellado, Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, UAM/Campus de Cantoblanco, E-28049 Madrid, Spain. Tel.: +34 91 585 4660; Fax: +34 91 372 0493; E-mail: mmellado@cnb.uam.es
Received 5 June 2003; Accepted 5 November 2003
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.
Keywords:
- AIDS,
- chemokine,
- chemokine receptor,
- HIV-1
