title: Gene therapy strategies to exploit TRIM derived restriction factors against HIV-1.
abstract: 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.
authors.affiliation: Centre for Gene Therapy, Institute of Child Health, University College London, London WC1N 1EH, UK. emma.chan@ucl.ac.uk.
authors.forename: Emma
authors.initials: E
authors.lastname: Chan
authors.affiliation: Centre for Gene Therapy, Institute of Child Health, University College London, London WC1N 1EH, UK. g.towers@ucl.ac.uk.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Towers
authors.affiliation: Centre for Gene Therapy, Institute of Child Health, University College London, London WC1N 1EH, UK. w.qasim@ucl.ac.uk.
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim
mesh_terms: D000090103:Antiviral Restriction Factors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D015658:HIV Infections / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases