Characterization of ovine TLR7 and TLR8 protein coding regions, detection of mutations and Maedi Visna virus infection

• Published in: Veterinary immunology and immunopathology Vol. 138; no. 1; pp. 51 - 59
• Main Authors: Mikula, Ivan, Bhide, Mangesh, Pastorekova, Silvia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2010; Amsterdam: Elsevier
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Animals; Base Sequence; Cattle; disease course; DNA Mutational Analysis; DNA Primers - genetics; Female; gene frequency; gene silencing; genes; Genetic Predisposition to Disease; Humans; immune system; immunity; immunosuppression (physiological); leucine; Maedi Visna virus; maedi-visna disease; missense mutation; Molecular Sequence Data; Mutation; Mutation, Missense; nucleotide sequences; pathogens; Pneumonia, Progressive Interstitial, of Sheep - genetics; Pneumonia, Progressive Interstitial, of Sheep - immunology; Point Mutation; protein secondary structure; Protein Structure, Secondary; receptors; Repetitive Sequences, Amino Acid; sequence analysis; sequence homology; Sequence Homology, Amino Acid; Sheep; Sheep - genetics; Sheep - immunology; TLR7; TLR8; Toll-like receptor 7; Toll-Like Receptor 7 - chemistry; Toll-Like Receptor 7 - genetics; Toll-like receptor 8; Toll-Like Receptor 8 - chemistry; Toll-Like Receptor 8 - genetics; Toll-like receptors; Visna - genetics; Visna - immunology; Visna maedi virus; Visna virus; OR; ECD; MV; LRR; SRLV; nBLAST; PAMP; TM; TLR8; Sheep; TLR7; TLR; Maedi Visna virus; Mutation; TIR
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2010.06.015

Toll-like receptors (TLRs) 2, 3, 4, 7, 8 and 9 play a crucial role in the recognition of viral entities and modulation of the innate immune system. This work presents sequence analysis of ovine TLR7 and TLR8 genes, depicts novel mutations and describes frequencies of mutations in Maedi Visna infected and healthy sheep. Totally 48 samples of the breed Tsigai were analyzed for the presence of mutations. Within 20 mutations, 14 were silent whereas 6 were missense. The frequencies of missense mutations in the Maedi Visna infected compared to non-infected sheep were: Lys115Glu ( P - 0.766, F-test), Asn117 ( P - 0.380) and Lys818Arg ( P - 0.739). These three mutations were localized in extra LRR (lucine rich repeat) region of TLR7, while mutation Ile73Leu ( P - 0.498) was located within LRR2 motif. Both mutations in TLR8, Asn165Lys ( P - 1.0) and Tyr349His ( P - 0.700), were present in extra LRR region. The secondary structure analysis of ovine TLR7 and TLR8 revealed conserved LRR motif structure, however with some irregularities compared to cattle and human. Transmembrane domains of TLR7 and TLR8 showed 100% homology between sheep and cattle wherein no mutations were found. In both TLRs TIR domains were highly conserved with occurrence of 4 silent mutations. Mutations in TLR7 and TLR8 may play an important role as predisposition factor for Maedi Visna infection. Considering the sequence homology among sheep, cattle and human genes encoding TLR7 and TLR8, we predict their similar function, localization and downstream signaling.