title: Blocking HIV-1 infection via CCR5 and CXCR4 receptors by acting in trans on the CCR2 chemokine receptor.
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.
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, UAM Campus de Cantoblanco, Madrid, Spain.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Rodríguez-Frade
authors.forename: Gustavo
authors.initials: G
authors.lastname: del Real
authors.forename: Antonio
authors.initials: A
authors.lastname: Serrano
authors.forename: Patricia
authors.initials: P
authors.lastname: Hernanz-Falcón
authors.forename: Silvia F
authors.initials: SF
authors.lastname: Soriano
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Vila-Coro
authors.forename: Ana Martín
authors.initials: AM
authors.lastname: de Ana
authors.forename: Pilar
authors.initials: P
authors.lastname: Lucas
authors.forename: Ignacio
authors.initials: I
authors.lastname: Prieto
authors.forename: Carlos
authors.initials: C
authors.lastname: Martínez-A
authors.forename: Mario
authors.initials: M
authors.lastname: Mellado
mesh_terms: D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000494:pharmacology; D019742:Chemokines, CC / Q000378:metabolism; D002633:Chemotaxis; D016895:Culture Media, Serum-Free; D019281:Dimerization; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D017930:Genes, Reporter; D015658:HIV Infections / Q000378:metabolism / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011233:Precipitin Tests; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2; D019742:Chemokines, CC; D016895:Culture Media, Serum-Free; D008024:Ligands; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D007532:Isoleucine; D002118:Calcium