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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 |
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author | Sharma, Adhikarimayum Lakhikumar Shaffer, Dylan Netting, Daniel Tyagi, Mudit |
author_facet | Sharma, Adhikarimayum Lakhikumar Shaffer, Dylan Netting, Daniel Tyagi, Mudit |
author_sort | Sharma, Adhikarimayum Lakhikumar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9722482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-97224822022-12-07 Cocaine sensitizes the CD4(+) T cells for HIV infection by co-stimulating NFAT and AP-1 Sharma, Adhikarimayum Lakhikumar Shaffer, Dylan Netting, Daniel Tyagi, Mudit iScience Article 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. Elsevier 2022-11-22 /pmc/articles/PMC9722482/ /pubmed/36483012 http://dx.doi.org/10.1016/j.isci.2022.105651 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Sharma, Adhikarimayum Lakhikumar Shaffer, Dylan Netting, Daniel Tyagi, Mudit Cocaine sensitizes the CD4(+) T cells for HIV infection by co-stimulating NFAT and AP-1 |
title | Cocaine sensitizes the CD4(+) T cells for HIV infection by co-stimulating NFAT and AP-1 |
title_full | Cocaine sensitizes the CD4(+) T cells for HIV infection by co-stimulating NFAT and AP-1 |
title_fullStr | Cocaine sensitizes the CD4(+) T cells for HIV infection by co-stimulating NFAT and AP-1 |
title_full_unstemmed | Cocaine sensitizes the CD4(+) T cells for HIV infection by co-stimulating NFAT and AP-1 |
title_short | Cocaine sensitizes the CD4(+) T cells for HIV infection by co-stimulating NFAT and AP-1 |
title_sort | cocaine sensitizes the cd4(+) t cells for hiv infection by co-stimulating nfat and ap-1 |
topic | Article |
url | 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 |
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