Background:  Host cell factors modulate retroviral infections. Among those, cyclophilin A (CypA) promotes virus infectivity by facilitating virus uncoating or capsid unfolding or by preventing retroviral capsid interaction with cellular restriction factors. In Aotus species, a retrotransposed copy of CypA inserted into the tripartite motif 5 (TRIM5) gene encodes a fusion protein which may block HIV-1 by targeting the incoming virus to ubiquitin-ligated degradation or by interfering with normal uncoating of the incoming particle, rendering those monkeys resistant to infection.

Methods:  In this study, we have extensively analyzed representative specimens from all 13 New World primate genera for the presence of CypA retrotransposition into TRIM5 gene. A polymerase chain reaction (PCR) assay was designed to discriminate DNA fragments between exons 7 and 8 of TRIM5 gene including (900 bp) or not (100 bp) the inserted CypA copy in the genomic DNA. CypA amino acid sequences generated were aligned in Clustal W and neighbor-joining phylogenetic inferences were conducted in MEGA and compared with those of cytochrome b genes. Positive selection in the CypA gene coding region was evaluated through PAML.

Results:  We showed that the retrotransposed CypA copy is present only in Aotus genus, and among all 4 species analyzed. We also showed that this inserted copy has diverged from its original counterpart, and that this occurred prior to Aotus radiation. CypA evolution occurred distinctively from cytochrome b gene. No positive selective pressure was observed in the retrotransposed CypA copy, either as whole or at any specific codon. Previous sequences reported as from A. trivirgatus clustered with A. lemurinus in our CypA gene analysis.

Conclusions:  TRIM5-Cyp is characteristic of Aotus genus, and the retrotransposition has happened before the genus radiation. Molecular evolution has diverged the CypA original and retrotransposed copies, likely through neutral selective pressure. Our data underscore the need for a precise taxonomic identification of primate species used as models for retroviral infections and novel antiviral approaches.