(Institución)

Digital.CSIC > Biología y Biomedicina > Centro Nacional de Biotecnología (CNB) > (CNB) Artículos >

Compartir

EndNote

Impacto

Artículos relacionados

Registro de acceso abierto The amino-terminal domain of the CCR2 chemokine receptor acts as coreceptor for HIV-1 infection

Autor :Frade, José M.R.
Llorente Gómez, María de las Mercedes
Mellado, Mario
Alcamí, José
Gutiérrez Ramos, José Carlos
Zaballos, Ángel
Real, Gustavo del
Martínez-Alonso, Carlos
Palabras clave :Chemokine receptor, HIV-1 coreceptor, Monoclonal antibodies
Fecha de publicación :ago-1997
Editor:American Society for Clinical Investigation
Citación :The Journal of Clinical Investigation, vol. 100(3), pp. 497-502, (1997)
Resumen:The chemokines are a homologous serum protein family characterized by their ability to induce activation of integrin adhesion molecules and leukocyte migration. Chemokines interact with their receptors, which are composed of a single-chain, seven-helix, membrane-spanning protein coupled to G proteins. Two CC chemokine receptors, CCR3 and CCR5, as well as the CXCR4 chemokine receptor, have been shown necessary for infection by several HIV-1 virus isolates. We studied the effect of the chemokine monocyte chemoattractant protein 1 (MCP-1) and of a panel of MCP-1 receptor (CCR2)-specific monoclonal antibodies (mAb) on the suppression of HIV-1 replication in peripheral blood mononuclear cells. We have compelling evidence that MCP-1 has potent HIV-1 suppressive activity when HIV-1–infected peripheral blood lymphocytes are used as target cells. Furthermore, mAb specific for the MCP-1R CCR2 which recognize the third extracellular CCR2 domain inhibit all MCP-1 activity and also block MCP-1 suppressive activity. Finally, a set of mAb specific for the CCR2 amino-terminal domain, one of which mimics MCP-1 activity, has a potent suppressive effect on HIV-1 replication in M- and T-tropic HIV-1 viral isolates. We conjecture a role for CCR2 as a coreceptor for HIV-1 infection and map the HIV-1 binding site to the amino-terminal part of this receptor. This concurs with results showing that the CCR5 amino terminus is relevant in HIV-1 infection, although chimeric fusion of various extracellular domains shows that other domains are also implicated. We discuss the importance of CCR2 structure relative to its coreceptor role and the role of anti-CCR2 receptor antibodies in the prevention of HIV-1 infection.
URI :http://hdl.handle.net/10261/3620
ISSN:0021-9738
DOI:10.1172/JCI119558.
Aparece en las colecciones: (CNB) Artículos

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.