TRIM5α polymorphism identification in cynomolgus macaques of Vietnamese origin and Chinese rhesus macaques

TRIM5α is a retroviral restriction factor, in which the B30.2 (SPRY) and coiled-coil domains cooperate to determine the specificity of TRIM5α-mediated capture of retroviral capsids. Here, all exons of TRIM5α were analyzed in 39 Vietnamese cynomolgus macaques (VCE) and 29 Chinese rhesus macaques (CR). Our results revealed the presence of 22 alleles using the PHASE 2.0 software package (PHylogenetics And Sequence Evolution), including two novel species-specific alleles with a low frequency in VCE in exons 4 and 8, which encoded the coiled-coil and B30.2 (SPRY) domains, respectively. Nine alleles were detected in both VCE and CR, while four alleles were likely shared between the species. Of these alleles, the highest frequencies of 38% and 26% occurred in VCE and CR, respectively. Importantly, we found that some alleles encoded the same coiled-coil domain, but not the SPRY domain. In contrast, other alleles encoded the same SPRY domain, but not the coiled-coil domain. Our findings will contribute to the understanding of the interaction between the two domains and the determination of the specificity of TRIM5α-mediated capture of retroviral capsids. Our results from the phylogenetic trees constructed for VCE and CR suggested that the macaques' ability to inhibit SIV replication became gradually stronger if they carried corresponding alleles in four clades (clades4-7). More interesting, in clade3, both novel allele pairs (4E100a, 10E147a) and allele pairs (7R17b and 13R11b), which had the strong ability to inhibit SIV replication, originated from the same ancestral allele, suggesting that the novel alleles might play a key role to determine an animal's ability to inhibit SIV/HIV replication. However, further studies are needed to increase our understanding of the genetic background of TRIM5α in these two macaque species.