title: Potent lentiviral restriction by a synthetic feline TRIM5 cyclophilin A fusion.
abstract: A synthetic feline TRIM5-cyclophilin A fusion protein (feTRIMCyp) was generated and transduced into feline cells. feTRIMCyp was highly efficient at preventing infection with human (HIV) and feline (FIV) immunodeficiency virus pseudotypes, and feTRIMCyp-expressing cells resisted productive infection with either FIV-Fca or FIV-Pco. The restriction of FIV infection by feTRIMCyp was reversed by the cyclosporine (Cs) derivatives NIM811 and Debio-025 but less so by Cs itself. FeTRIMCyp and FIV infections of the cat offer a unique opportunity to evaluate TRIMCyp-based approaches to genetic therapy for HIV infection and the treatment of AIDS.
authors.affiliation: Retrovirus Research Laboratory, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, United Kingdom.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dietrich
authors.forename: Angela
authors.initials: A
authors.lastname: Macintyre
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McMonagle
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Price
authors.forename: Leo C
authors.initials: LC
authors.lastname: James
authors.forename: William A
authors.initials: WA
authors.lastname: McEwan
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Hosie
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Willett
mesh_terms: D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D002415:Cats; D002460:Cell Line; D021984:Cyclophilin A / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D016181:Feline Acquired Immunodeficiency Syndrome / Q000517:prevention & control / Q000821:virology*; D015658:HIV Infections / Q000517:prevention & control / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D053586:Virus Internalization
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A