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Cannabinoid receptor 2-mediated attenuation of CXCR4-tropic HIV infection in primary CD4+ T cells.
Costantino, Cristina Maria; Gupta, Achla; Yewdall, Alice W; Dale, Benjamin M; Devi, Lakshmi A; Chen, Benjamin K.
Afiliación
  • Costantino CM; Department of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, New York, United States of America.
PLoS One ; 7(3): e33961, 2012.
Article en En | MEDLINE | ID: mdl-22448282
Agents that activate cannabinoid receptor pathways have been tested as treatments for cachexia, nausea or neuropathic pain in HIV-1/AIDS patients. The cannabinoid receptors (CB(1)R and CB(2)R) and the HIV-1 co-receptors, CCR5 and CXCR4, all signal via Gαi-coupled pathways. We hypothesized that drugs targeting cannabinoid receptors modulate chemokine co-receptor function and regulate HIV-1 infectivity. We found that agonism of CB(2)R, but not CB(1)R, reduced infection in primary CD4+ T cells following cell-free and cell-to-cell transmission of CXCR4-tropic virus. As this change in viral permissiveness was most pronounced in unstimulated T cells, we investigated the effect of CB(2)R agonism on to CXCR4-induced signaling following binding of chemokine or virus to the co-receptor. We found that CB(2)R agonism decreased CXCR4-activation mediated G-protein activity and MAPK phosphorylation. Furthermore, CB(2)R agonism altered the cytoskeletal architecture of resting CD4+ T cells by decreasing F-actin levels. Our findings suggest that CB(2)R activation in CD4+ T cells can inhibit actin reorganization and impair productive infection following cell-free or cell-associated viral acquisition of CXCR4-tropic HIV-1 in resting cells. Therefore, the clinical use of CB(2)R agonists in the treatment of AIDS symptoms may also exert beneficial adjunctive antiviral effects against CXCR4-tropic viruses in late stages of HIV-1 infection.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Cannabinoides / Linfocitos T CD4-Positivos / Infecciones por VIH / Receptores CXCR4 / Receptor Cannabinoide CB2 Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2012 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Cannabinoides / Linfocitos T CD4-Positivos / Infecciones por VIH / Receptores CXCR4 / Receptor Cannabinoide CB2 Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2012 Tipo del documento: Article