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Cocaine sensitizes the CD4(+) T cells for HIV infection by co-stimulating NFAT and AP-1
The productive infection of HIV, which generates new viral progeny, depends on the activation status of the cell. In this study, we found cocaine exposure sensitizes partially active CD4(+) T cells and makes them poised for productive HIV infection. We discovered that cocaine treatment enhances the...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9722482/ https://www.ncbi.nlm.nih.gov/pubmed/36483012 http://dx.doi.org/10.1016/j.isci.2022.105651 |
Sumario: | The productive infection of HIV, which generates new viral progeny, depends on the activation status of the cell. In this study, we found cocaine exposure sensitizes partially active CD4(+) T cells and makes them poised for productive HIV infection. We discovered that cocaine treatment enhances the metabolic state of the cells by co-stimulating several transcription factors, mainly NFAT and AP-1, the two transcription factors, which specifically play a crucial role in enhancing both HIV and the overall cellular gene expression in T cells. We found that cocaine-induced AP-1 works in tandem with NFAT to boost HIV transcription. The enhanced HIV transcription upon cocaine exposure was further confirmed through higher phosphorylation of the crucial serine residues at the carboxyl-terminal domain (CTD) of RNA polymerase II. The insights gained from this study could aid in developing highly specialized therapeutics combating the deleterious effects of cocaine on the cocaine-using HIV population. |
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