{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:58:13Z","timestamp":1776405493671,"version":"3.51.2"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"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. Immunol."],"abstract":"<jats:p>\n                    Four decades into the HIV pandemic, HIV-2 infection remains an underutilized comparative resource for HIV-1 cure research. HIV-2 is associated with lower plasma viral loads, slower CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell decline, and delayed disease progression in many individuals. Early studies attributed these features to intrinsic viral attenuation, pointing to differences in accessory protein function, transcriptional regulation, and reservoir size. However, accumulating molecular and epidemiological evidence challenges this interpretation. The transcriptional status of HIV-2\n                    <jats:italic>in vivo<\/jats:italic>\n                    is not uniform across studies. Some studies report comparable viral RNA levels between HIV-1 and HIV-2 in CD4-matched individuals. In contrast, others find lower per-cell transcriptional output in HIV-2, suggesting that the degree of transcriptional restriction varies with cohort composition, disease stage, and measurement approach. Importantly, neither finding supports a model of uniform proviral silencing. This review examines the molecular biology, immune responses, and reservoir dynamics of HIV-2 infection, weighing evidence that both supports and challenges the view of HIV-2 as an attenuated comparator to HIV-1. The available data suggest that HIV-2 persistence involves regulated viral expression and ongoing, albeit attenuated, immune engagement, rather than transcriptional silence. However, the extent to which immune activation in HIV-2 is quantitatively or qualitatively distinct from that in HIV-1 remains incompletely resolved. HIV-2 does not provide a prescriptive cure blueprint, but it reveals a key biological constraint: ongoing viral transcription can coexist with prolonged immune containment. This finding argues against transcription-only approaches to HIV-1 remission and underscores the need for strategies that combine transcriptional modulation with sustained immune engagement.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1825935","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:22:16Z","timestamp":1776403336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["HIV-2 infection as a comparative lens for functional HIV-1 remission"],"prefix":"10.3389","volume":"17","author":[{"given":"Sabastine Eugene","family":"Arthur","sequence":"first","affiliation":[{"name":"Medical and Scientific Research Centre, University of Ghana Medical Centre","place":["Accra, Ghana"]},{"name":"Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana","place":["Accra, Ghana"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Atanniba","sequence":"additional","affiliation":[{"name":"Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana","place":["Accra, Ghana"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prince Adom","family":"Nartey","sequence":"additional","affiliation":[{"name":"Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana","place":["Accra, Ghana"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeena Abla","family":"Tay","sequence":"additional","affiliation":[{"name":"Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana","place":["Accra, Ghana"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dzidzor Aku","family":"Attoh","sequence":"additional","affiliation":[{"name":"Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana","place":["Accra, Ghana"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher Zaab-Yen","family":"Abana","sequence":"additional","affiliation":[{"name":"Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana","place":["Accra, Ghana"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn Yayra","family":"Bonney","sequence":"additional","affiliation":[{"name":"Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana","place":["Accra, Ghana"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George Boateng","family":"Kyei","sequence":"additional","affiliation":[{"name":"Medical and Scientific Research Centre, University of Ghana Medical Centre","place":["Accra, Ghana"]},{"name":"Department of Virology, Noguchi Memorial Institute for Medical Research, University of Ghana","place":["Accra, Ghana"]},{"name":"Departments of Medicine and Molecular Microbiology, Washington University School of Medicine in St. Louis","place":["St. Louis, MO, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.1739","article-title":"Comparing HIV\u20101 and HIV\u20102 infection: Lessons for viral immunopathogenesis","volume":"23","author":"Nyamweya","year":"2013","journal-title":"Rev Med Virol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0129886","article-title":"Plasma HIV-2 RNA according to CD4 count strata among HIV-2-infected adults in the IeDEA West Africa Collaboration","volume":"10","author":"Ekou\u00e9vi","year":"2015","journal-title":"PloS One"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1016\/B978-1-4160-2882-6.50060-5","article-title":"Epidemiology, natural history and treatment of HIV-2 infections","volume-title":"Glob. 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