Blocking HIV-1 infection via CCR5 and CXCR4 receptors by acting in trans on the CCR2 chemokine receptor.
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.
Rodríguez-Frade
José Miguel
JM
Department of Immunology and Oncology, Centro Nacional de Biotecnología, UAM Campus de Cantoblanco, Madrid, Spain.
del Real
Gustavo
G
Serrano
Antonio
A
Hernanz-Falcón
Patricia
P
Soriano
Silvia F
SF
Vila-Coro
Antonio J
AJ
de Ana
Ana Martín
AM
Lucas
Pilar
P
Prieto
Ignacio
I
Martínez-A
Carlos
C
Mellado
Mario
M
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
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