{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T21:08:02Z","timestamp":1784668082444,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute for Alergy and Infectious Diseases","award":["R01AI150469"],"award-info":[{"award-number":["R01AI150469"]}]},{"name":"National Institute for Alergy and Infectious Diseases","award":["R01GM123973"],"award-info":[{"award-number":["R01GM123973"]}]},{"name":"National Institute for General Medical Sciences","award":["R01AI150469"],"award-info":[{"award-number":["R01AI150469"]}]},{"name":"National Institute for General Medical Sciences","award":["R01GM123973"],"award-info":[{"award-number":["R01GM123973"]}]},{"name":"CWRU funds","award":["R01AI150469"],"award-info":[{"award-number":["R01AI150469"]}]},{"name":"CWRU funds","award":["R01GM123973"],"award-info":[{"award-number":["R01GM123973"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Vpr, a virion-associated accessory virulence factor of HIV-1, promotes virus replication in both T cells and macrophages. Although Vpr\u2019s early activity\u2014antagonism of preintegration silencing and host restriction factors\u2014has been documented, the relative contribution of virion-associated versus de novo expressed Vpr to HIV-1 replication fitness remains unclear. Here, we developed a T cell-based system that genetically separates early and late Vpr functions by combining tetracycline-inducible Vpr expression in CEM.SS T cells with vpr-deficient HIV-1 constructs and Gag p6 mutations that block Vpr packaging. CEM.SS T cells have been shown to recapitulate the positive effect of Vpr on HIV-1 replication observed in activated primary T cells. Using pairwise replication fitness assays under spreading infection conditions, we demonstrate that de novo synthesized Vpr exerts the dominant effect on HIV-1 replication in T cells, while virion-associated Vpr plays a lesser role. Somewhat unexpectedly, our findings reveal that antagonism of preintegration HIV-1 silencing by virion-associated Vpr is unlikely to be the major driver of enhanced HIV-1 replication in proliferating T cells. Instead, this function may play a more prominent role in the infection of non-dividing T cells and\/or other cell types.<\/jats:p>","DOI":"10.3390\/v17070958","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T11:19:27Z","timestamp":1751887167000},"page":"958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["De Novo Expressed Vpr Stimulates HIV-1 Replication in T Cells"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5983-1058","authenticated-orcid":false,"given":"Blessing","family":"Enya","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Case Western Reserve School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7417-0764","authenticated-orcid":false,"given":"Jacek","family":"Skowronski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Case Western Reserve School of Medicine, 10900 Euclid Ave., Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rashid, F., Xie, Z., Suleman, M., Shah, A., Khan, S., and Luo, S. 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