689. Restriction Profiles of Primate TRIM5α on FIV

Abstract

TRIM5α is a dominant repressive factor against retrovirus infection. Different species variants of TRIM5α have unique patterns of restriction against lentiviruses and oncoretroviruses. Human TRIM5α (TRIM5αhu) has been shown to effectively inhibit N tropic MLV (N-MLV) but have little effect against human immunodeficiency virus type 1 (HIV-1). Non-human primate species variants of TRIM5α display strong viral restriction against HIV-1. A recent publication (Saenz et al. J Virol., 2005 Dec;79(24):15175-88) detailed the restrictive properties of human and rhesus monkey TRIM5α against FIV when exogenously expressed in the feline cell line CrFK, but saw no restriction in the D17 canine cell line. Using stable mouse cell lines expressing species variants of TRIM5α, we observed no restriction of FIV by TRIM5αhu while both rhesus and African green monkey (AGM) TRIM5α display significant viral inhibition. Additionally, a human TRIM5α chimera containing the restrictive SPRY domain residues from rhesus displayed considerable inhibition of FIV similar to what has been observed with HIV-1. These findings suggest that HIV-1 and FIV capsids pose similar targets for TRIM5α. Ongoing experiments are investigating the restrictive capabilities of endogenous TRIM5αhu on FIV and HIV in several human cell types. Microarray analysis and RT-PCR of several human tissues and cell lines suggest differential expression of TRIM5. The results from this study have implications for the utility of FIV as a gene transfer vector in humans and non-human primates.