Potent lentiviral restriction by a synthetic feline TRIM5 cyclophilin A fusion.
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.
Dietrich
Isabelle
I
Retrovirus Research Laboratory, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, United Kingdom.
Macintyre
Angela
A
McMonagle
Elizabeth
E
Price
Amanda J
AJ
James
Leo C
LC
McEwan
William A
WA
Hosie
Margaret J
MJ
Willett
Brian J
BJ
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
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