{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:43:08Z","timestamp":1793043788795,"version":"4.5.0"},"reference-count":237,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T00:00:00Z","timestamp":1613692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["91718331"],"award-info":[{"award-number":["91718331"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human immunodeficiency virus-1 (HIV-1) persists as a global health concern, with an incidence rate of approximately 2 million, and estimated global prevalence of over 35 million. Combination antiretroviral treatment is highly effective, but HIV-1 patients that have been treated still suffer from chronic inflammation and residual viral replication. It is therefore paramount to identify therapeutically efficacious strategies to eradicate viral reservoirs and ultimately develop a cure for HIV-1. It has been long accepted that the restriction factor tripartite motif protein 5 isoform alpha (TRIM5\u03b1) restricts HIV-1 infection in a species-specific manner, with rhesus macaque TRIM5\u03b1 strongly restricting HIV-1, and human TRIM5\u03b1 having a minimal restriction capacity. However, several recent studies underscore human TRIM5\u03b1 as a cell-dependent HIV-1 restriction factor. Here, we present an overview of the latest research on human TRIM5\u03b1 and propose a novel conceptualization of TRIM5\u03b1 as a restriction factor with a varied portfolio of antiviral functions, including mediating HIV-1 degradation through autophagy- and proteasome-mediated mechanisms, and acting as a viral sensor and effector of antiviral signaling. We have also expanded on the protective antiviral roles of autophagy and outline the therapeutic potential of autophagy modulation to intervene in chronic HIV-1 infection.<\/jats:p>","DOI":"10.3390\/v13020320","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T20:54:08Z","timestamp":1613768048000},"page":"320","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Human TRIM5\u03b1: Autophagy Connects Cell-Intrinsic HIV-1 Restriction and Innate Immune Sensor Functioning"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9850-9643","authenticated-orcid":false,"given":"Alexandra P. M.","family":"Cloherty","sequence":"first","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam Institute for Infection &amp; Immunity, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4889-3691","authenticated-orcid":false,"given":"Anusca G.","family":"Rader","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam Institute for Infection &amp; Immunity, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Compeer","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam Institute for Infection &amp; Immunity, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5682-4143","authenticated-orcid":false,"given":"Carla M. S.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Amsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Amsterdam Institute for Infection &amp; Immunity, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2020, October 19). HIV\/AIDS Factsheets. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hiv-aids."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"HIV CAUSAL Collaboration, Ray, M., Logan, R., Sterne, J.A.C., Hern\u00e1ndez-D\u00edaz, S., Robins, J.M., Sabin, C., Bansi, L., van Sighem, A., and de Wolf, F. (2010). The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. 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