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Background  Since the first report of the antiretroviral restriction factor TRIM5α in primates, several orthologs in other mammals have been described. Recent studies suggest that leporid retroviruses like RELIK, the first reported endogenous lentivirus ever, may have imposed positive selection in  TRIM5α  orthologs of the European rabbit and European brown hare. Considering that RELIK must already have been present in a common ancestor of the leporid genera  Lepus ,  Sylvilagus  and  Oryctolagus , we extended the study of evolutionary patterns of TRIM5α to other members of the Leporidae family, particularly to the genus  Sylvilagus . Therefore, we obtained the  TRIM5α  nucleotide sequences of additional subspecies and species of the three leporid genera. We also compared lagomorph TRIM5α deduced protein sequences and established  TRIM5α  gene and TRIM5α protein phylogenies.    Results  The deduced protein sequence of Iberian hare TRIM5α was 89% identical to European rabbit TRIM5α, although high divergence was observed at the PRYSPRY v1 region between rabbit and the identified alleles from this hare species (allele 1: 50% divergence; allele 2: 53% divergence). A high identity was expected between the  Sylvilagus  and  Oryctolagus  TRIM5α proteins and, in fact, the  Sylvilagus  TRIM5α was 91% identical to the  Oryctolagus  protein. Nevertheless, the PRYSPRY v1 region was only 50% similar between these genera. Selection analysis of Lagomorpha TRIM5α proteins identified 25 positively-selected codons, 11 of which are located in the PRYSPRY v1 region, responsible for species specific differences in viral capsid recognition.    Conclusions  By extending Lagomorpha TRIM5α studies to an additional genus known to bear RELIK, we verified that the divergent species-specific pattern observed between the  Oryctolagus  and  Lepus  PRYSPRY-domains is also present in  Sylvilagus  TRIM5α. This work is one of the first known studies that compare the evolution of the antiretroviral restriction factor TRIM5α in different mammalian groups, Lagomorpha and Primates.

Study of Sylvilagusrabbit TRIM5α species-specific domain: how ancient endoviruses could have shaped the antiviral repertoire in Lagomorpha