Document Type

Article

Publication Date

12-22-2022

Comments

This article is the author’s final published version in Science, Volume 25, Issue 12, December 2022, Article number 105651.

The published version is available at https://doi.org/10.1016/j.isci.2022.105651. Copyright © Sharma et al.

Abstract

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.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

PubMed ID

36483012

Language

English

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