{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:35:44Z","timestamp":1791192944972,"version":"4.1.0"},"reference-count":140,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2014,1,14]],"date-time":"2014-01-14T00:00:00Z","timestamp":1389657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Restriction factors are a collection of antiviral proteins that form an important aspect of the innate immune system. Their constitutive expression allows immediate response to viral infection, ahead of other innate or adaptive immune responses. We review the molecular mechanism of restriction for four categories of restriction factors; TRIM5, tetherin, APOBEC3G and SAMHD1 and go on to consider how the TRIM5 and TRIMCyp proteins in particular, show promise for exploitation using gene therapy strategies. Such approaches could form an important alternative to current anti-HIV-1 drug regimens, especially if combined with strategies to eradicate HIV reservoirs. Autologous CD4+ T cells or their haematopoietic stem cell precursors engineered to express TRIMCyp restriction factors, and provided in a single therapeutic intervention could then be used to restore functional immunity with a pool of cells protected against HIV. We consider the challenges ahead and consider how early clinical phase testing may best be achieved.<\/jats:p>","DOI":"10.3390\/v6010243","type":"journal-article","created":{"date-parts":[[2014,1,14]],"date-time":"2014-01-14T11:21:38Z","timestamp":1389698498000},"page":"243-263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Gene Therapy Strategies to Exploit TRIM Derived Restriction Factors against HIV-1"],"prefix":"10.3390","volume":"6","author":[{"given":"Emma","family":"Chan","sequence":"first","affiliation":[{"name":"Centre for Gene Therapy, Institute of Child Health, University College London, London WC1N 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Towers","sequence":"additional","affiliation":[{"name":"MRC Centre for Medical Molecular Virology, University College London, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waseem","family":"Qasim","sequence":"additional","affiliation":[{"name":"Centre for Gene Therapy, Institute of Child Health, University College London, London WC1N 1EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1182\/blood.V96.3.785.015k10_785_793","article-title":"Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta gene-modified autologous CD4+ and CD8+ T cells in human immunodeficiency virus-infected subjects","volume":"96","author":"Mitsuyasu","year":"2000","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1006\/mthe.2002.0611","article-title":"A Phase II randomized study of HIV-specific T-cell gene therapy in subjects with undetectable plasma viremia on combination antiretroviral therapy","volume":"5","author":"Deeks","year":"2002","journal-title":"Mol. 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