Functional characterization of genetic variants in the porcine TLR3 gene.

Toll-like receptor 3 (TLR3) recognizes double-stranded RNA, which is a molecular signature of viruses, and plays a pivotal role in host defense against viral invasion. Polymorphisms in the human TLR3 gene have been shown to affect the receptor function and to be associated with a variety of diseases, suggesting correlations between TLR3 polymorphisms and the disease resistance/susceptibility in pigs. In this study, 5 known non-synonymous single nucleotide polymorphisms (SNPs) in the coding sequences of the porcine TLR3 gene - c.800C>T (p.T267M), c.933A>G (p.I311M), c.1116A>T (p.K372N), c.2129C>G (p.T710S), and c.2160T>G (p.I720M) - were analyzed for their effect on receptor function in transiently transfected PK-15 cells by using a luciferase reporter assay. In addition, the distribution of SNP c.933A>G was analyzed among pig populations. SNP c.933A>G significantly decreased the response to poly(I:C) (P < 0.05), as represented by the weaker induction of firefly luciferase relative to that achieved by wild-type TLR3. SNP c.933A>G results in the alteration of conserved amino acids in the highly conserved segment of the 12th leucine repeat region and is conserved among TLR3 orthologs from fishes to primates. Moreover, together with the results of previous studies, the results of the present study revealed that SNP c.933A>G is found solely in local Chinese pig breeds. These results suggested that SNP c.933A>G plays a role in porcine disease resistance/susceptibility.

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