Abstract
BackgroundSince 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.ResultsThe 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.ConclusionsBy 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.
Highlights
Since the first report of the antiretroviral restriction factor TRIM5a in primates, several orthologs in other mammals have been described
TRIM5a divergence and phylogeny in Lagomorpha In this study, all the deduced TRIM5a protein sequences obtained from leporids were aligned and compared to that previously described for the European rabbit [38] (Figure 1)
To more completely assess the TRIM5a gene in the Lagomorpha order, we included American pika (Ochotona princeps) TRIM5a nucleotide sequence retrieved from the whole genome shotgun (WGS) project
Summary
Since the first report of the antiretroviral restriction factor TRIM5a in primates, several orthologs in other mammals have been described. The intense study of lentiviruses in the past 30 years, especially of human immunodeficiency viruses (HIV-1 and HIV-2), has been more recently accompanied by de Matos et al BMC Evolutionary Biology 2011, 11:294 http://www.biomedcentral.com/1471-2148/11/294 the study of antiretroviral restriction factors, like the TRIM5a protein, one of the members of TRIM family [7,8,9,10,11]. TRIM5a is the largest isoform encoded by the TRIM5 gene and restricts infection by HIV-1 and other retroviruses, dependent on a speciesspecific sequence variation in the PRYSPRY domain, upon entry into the host cell cytoplasm and prior to reverse transcription [7,8]. The PRYSPRY domain binds to the viral capsid, and the domain sequence variation determines the restriction specificity [17,18,24,25,26]. TRIM5a spontaneously forms a hexagonal lattice complementary to the capsid lattice, a molecular signature of retroviruses, which greatly stimulates TRIM5a lattice formation [29,30]
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