{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:52:00Z","timestamp":1790711520424,"version":"4.1.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Illicit drug use, particularly the synthetic opioid fentanyl, presents a significant global health challenge. Previous studies have shown that fentanyl enhances viral replication; yet, the mechanisms by which it affects HIV pathogenesis remain unclear. This study investigated the impact of fentanyl on HIV replication in CD4<jats:sup>+<\/jats:sup> T lymphocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CD4<jats:sup>+<\/jats:sup> T lymphocytes from HIV-negative donors were activated, infected with HIV<jats:sub>NL4-3<\/jats:sub>, and treated with fentanyl. HIV proviral DNA and p24 antigen expression were quantified using real-time PCR and ELISA, respectively. Single-cell RNA libraries were analyzed to identify differentially expressed genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Results indicated that fentanyl treatment increased HIV p24 expression and proviral DNA levels, and naltrexone mitigated these effects. Single-cell RNAseq analysis identified significantly altered gene expression in CD4<jats:sup>+<\/jats:sup> T lymphocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results of our findings suggest that fentanyl promotes HIV replication <jats:italic>ex vivo<\/jats:italic>, emphasizing the need for a deeper understanding of opioid-virus interactions to develop better treatment strategies for individuals with HIV and opioid use disorder.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1463441","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T12:28:20Z","timestamp":1727267300000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Effect of fentanyl on HIV expression in peripheral blood mononuclear cells"],"prefix":"10.3389","volume":"15","author":[{"given":"Janani Madhuravasal","family":"Krishnan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna M.","family":"Roskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi L.","family":"Meeds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason T.","family":"Blackard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"ref1","author":"Abuse","year":"2020"},{"key":"ref2","doi-asserted-by":"crossref","DOI":"10.5772\/53010","article-title":"Immune responses and cell signaling during chronic HIV infection","volume-title":"Current perspectives in HIV infection","author":"Alhetheel","year":"2013"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"108321","DOI":"10.1016\/j.drugalcdep.2020.108321","article-title":"Opioid-related overdose mortality in the era of fentanyl: monitoring a shifting epidemic by person, place, and time","volume":"216","author":"Althoff","year":"2020","journal-title":"Drug Alcohol Depend."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e83207","DOI":"10.7554\/eLife.83207","article-title":"The anti-caspase 1 inhibitor VX-765 reduces immune activation, CD4+ T cell depletion, viral load, and total HIV-1 DNA in HIV-1 infected humanized mice","volume":"12","author":"Amand","year":"2023","journal-title":"eLife"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"444a","DOI":"10.1016\/j.bpj.2019.11.2487","article-title":"C subunit of the ATP synthase is an amyloidogenic channel-forming peptide: possible implications in mitochondrial pathogenesis","volume":"118","author":"Amodeo","year":"2020","journal-title":"Biophys. 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