{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T04:29:36Z","timestamp":1783052976429,"version":"3.54.6"},"reference-count":80,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":49,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health grants","doi-asserted-by":"crossref","award":["R01AI148084,R01AI149669,AI148084-S1,T32-AI007413,F31AI131957,F31AI15504,T32GM007315"],"award-info":[{"award-number":["R01AI148084,R01AI149669,AI148084-S1,T32-AI007413,F31AI131957,F31AI15504,T32GM007315"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"crossref","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,23]]},"abstract":"<jats:p>\n                    Despite effective treatment, human immunodeficiency virus (HIV) persists in optimally treated people as a transcriptionally silent provirus. Latently infected cells evade the immune system and the harmful effects of the virus, thereby creating a long-lasting reservoir of HIV. To gain a deeper insight into the molecular mechanisms of HIV latency establishment, we constructed a series of HIV-1 fluorescent reporter viruses that distinguish active versus latent infection. We unexpectedly observed that the proportion of active to latent infection depended on a limiting viral factor, which created a bottleneck that could be overcome by superinfection of the cell, T cell activation, or overexpression of HIV-1 transactivator of transcription (Tat). In addition, we found that\n                    <jats:italic>tat<\/jats:italic>\n                    and regulator of expression of virion proteins (Rev) expression levels varied among HIV molecular clones and that\n                    <jats:italic>tat<\/jats:italic>\n                    levels were an important variable in latency establishment. Lower\n                    <jats:italic>rev<\/jats:italic>\n                    levels limited viral protein expression whereas lower Tat levels or mutation of the Tat binding element promoted latent infection that was resistant to reactivation even in fully activated primary T cells. Nevertheless, we found that combinations of latency reversal agents targeting both cellular activation and histone acetylation pathways overcame deficiencies in the Tat\/TAR axis of transcription regulation. These results provide additional insight into the mechanisms of latency establishment and inform Tat-centered approaches to cure HIV.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.184711","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T12:00:27Z","timestamp":1733400027000},"source":"Crossref","is-referenced-by-count":5,"title":["Variation in HIV-1 Tat activity is a key determinant in the establishment of latent infection"],"prefix":"10.1172","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8369-3361","authenticated-orcid":true,"given":"Francisco","family":"Gomez-Rivera","sequence":"first","affiliation":[{"name":"Graduate Program in Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeri H.","family":"Terry","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark M.","family":"Painter","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria C.","family":"Virgilio","sequence":"additional","affiliation":[{"name":"Department of Computational Medicine and Bioinformatics,"},{"name":"Cellular and Molecular Biology Program, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne E.","family":"Yaple-Maresh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1712-5809","authenticated-orcid":true,"given":"Kathleen L.","family":"Collins","sequence":"additional","affiliation":[{"name":"Graduate Program in Immunology,"},{"name":"Department of Internal Medicine,"},{"name":"Cellular and Molecular Biology Program, and"},{"name":"Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"B1","unstructured":"World Health Organization. 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