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Study of Sylvilagus rabbit TRIM5? species-specific domain: how ancient endoviruses could have shaped the antiviral repertoire in Lagomorpha.

ABSTRACT: BACKGROUND: Since the first report of the antiretroviral restriction factor TRIM5? 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 TRIM5? 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 TRIM5? to other members of the Leporidae family, particularly to the genus Sylvilagus. Therefore, we obtained the TRIM5? nucleotide sequences of additional subspecies and species of the three leporid genera. We also compared lagomorph TRIM5? deduced protein sequences and established TRIM5? gene and TRIM5? protein phylogenies. RESULTS: The deduced protein sequence of Iberian hare TRIM5? was 89% identical to European rabbit TRIM5?, 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 TRIM5? proteins and, in fact, the Sylvilagus TRIM5? was 91% identical to the Oryctolagus protein. Nevertheless, the PRYSPRY v1 region was only 50% similar between these genera. Selection analysis of Lagomorpha TRIM5? 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 TRIM5? 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 TRIM5?. This work is one of the first known studies that compare the evolution of the antiretroviral restriction factor TRIM5? in different mammalian groups, Lagomorpha and Primates.

SUBMITTER: de Matos AL

PROVIDER: S-EPMC3208668 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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

de Matos Ana Lemos AL van der Loo Wessel W Areal Helena H Lanning Dennis K DK Esteves Pedro J PJ

BMC evolutionary biology 20111008

<h4>Background</h4>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 Oryctolagu ...[more]

PMID: 21982459

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Project description:BACKGROUND: Recent studies in human have highlighted the importance of the monocyte chemotactic proteins (MCP) in leukocyte trafficking and their effects in inflammatory processes, tumor progression, and HIV-1 infection. In European rabbit (Oryctolagus cuniculus) one of the prime MCP targets, the chemokine receptor CCR5 underwent a unique structural alteration. Until now, no homologue of MCP-2/CCL8a, MCP-3/CCL7 or MCP-4/CCL13 genes have been reported for this species. This is interesting, because at least the first two genes are expressed in most, if not all, mammals studied, and appear to be implicated in a variety of important chemokine ligand-receptor interactions. By assessing the Rabbit Whole Genome Sequence (WGS) data we have searched for orthologs of the mammalian genes of the MCP-Eotaxin cluster. RESULTS: We have localized the orthologs of these chemokine genes in the genome of European rabbit and compared them to those of leporid genera which do (i.e. Oryctolagus and Bunolagus) or do not share the CCR5 alteration with European rabbit (i.e. Lepus and Sylvilagus). Of the Rabbit orthologs of the CCL8, CCL7, and CCL13 genes only the last two were potentially functional, although showing some structural anomalies at the protein level. The ortholog of MCP-2/CCL8 appeared to be pseudogenized by deleterious nucleotide substitutions affecting exon1 and exon2. By analyzing both genomic and cDNA products, these studies were extended to wild specimens of four genera of the Leporidae family: Oryctolagus, Bunolagus, Lepus, and Sylvilagus. It appeared that the anomalies of the MCP-3/CCL7 and MCP-4/CCL13 proteins are shared among the different species of leporids. In contrast, whereas MCP-2/CCL8 was pseudogenized in every studied specimen of the Oryctolagus - Bunolagus lineage, this gene was intact in species of the Lepus - Sylvilagus lineage, and was, at least in Lepus, correctly transcribed. CONCLUSION: The biological function of a gene was often revealed in situations of dysfunction or gene loss. Infections with Myxoma virus (MYXV) tend to be fatal in European rabbit (genus Oryctolagus), while being harmless in Hares (genus Lepus) and benign in Cottontail rabbit (genus Sylvilagus), the natural hosts of the virus. This communication should stimulate research on a possible role of MCP-2/CCL8 in poxvirus related pathogenicity.

Dataset Information

Study of Sylvilagus rabbit TRIM5? species-specific domain: how ancient endoviruses could have shaped the antiviral repertoire in Lagomorpha.

Publications

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

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