TRIM5α does not affect simian immunodeficiency virus SIV _mac251 replication in vaccinated or unvaccinated Indian Rhesus Macaques following intrarectal challenge exposure

TRIM5α is a natural resistance factor that binds retroviral capsid proteins and restricts virus replication. The B30.2/SPRY domain of TRIM5α is polymorphic in rhesus macaques, and some alleles are associated with reduced simian immunodeficiency virus (SIV) SIV _mac251 and SIV _smE543 replication in vivo. We determined the distribution of TRIM5α alleles by PCR and sequence analysis of the B30.2/SPRY domain in a cohort of 82 macaques. Thirty-nine of these macaques were mock vaccinated, 43 were vaccinated with either DNA-SIV/ ALVAC-SIV/gp120, ALVAC-SIV/gp120, or gp120 alone, and all were exposed intrarectally to SIV _mac251 at one of three doses. We assessed whether the TRIM5α genotype of the macaques affected the replication of challenge virus by studying the number of SIV variantstransmitted, the number of exposures required, the SIV _mac251 viral level in plasma and tissue, and the CD4 ⁺ T-cell counts. Our results demonstrated that TRIM5α alleles, previously identified as restrictive for SIV _mac251 replication in vivo following intravenous exposure, did not affect SIV _mac251 replication following mucosal exposure, regardless of prior vaccination, challenge dose, or the presence of the protective major histocompatibility complex alleles (MamuA01 ⁺, MamuB08 ⁺,or MamuB017 ⁺). The TRIM5α genotype had no apparent effect on the number of transmitted variants or the number of challenge exposures necessary to infect the animals. DNA sequencing of the SIV _mac251 Gag gene of the two stocks used in our study revealed SIV _mac239-like sequences that are predicted to be resistant to TRIM5α restriction. Thus, the TRIM5α genotype does not confound results of mucosal infection of rhesus macaques with SIV _mac251.