Korean Journal of Poultry Science (한국가금학회지)

The Korean Society of Poultry Science (한국가금학회)
권호 표지
DOI QR코드

DOI QR Code

In Silico Evaluation of Deleterious SNPs in Chicken TLR3 and TLR4 Genes

  • Shin, Donghyun (Department of Animal Biotechnology, Chonbuk National University) ;
  • Song, Ki-Duk (Department of Animal Biotechnology, Chonbuk National University)
  • Received : 2018.07.23
  • Accepted : 2018.09.07
  • Published : 2018.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

The innate immune recognition is based on the detection of microbial products. Toll-like receptors (TLRs) located on the cell surface and the endosome senses microbial components and nucleic acids, respectively. Chicken TLRs mediate immune responses by sensing ligands from pathogens, have been studied as immune adjuvants to increase the efficacy of vaccines. Single nucleotide polymorphisms (SNPs) of TLR3 and TLR4 genes in chicken were associated with resistance and susceptibility to viral infection. In this study, SNPs of chTLR3 and chTLR4 genes were retrieved from public database and annotated with chicken reference genome. Three-dimensional models of the chTLR3 and chTLR4 proteins were built using a Swiss modeler. We identified 35 and 13 nsSNPs in chTLR3 and chTLR4 genes respectively. Sorting Intolerant from Tolerant (SIFT) and Polymorphism Phenotyping v2 (Polyphen-2) analyses, suggested that, out of 35 and 13 nsSNPs, 4 and 2 SNPs were identified to be deleterious in chTLR3 and chTLR4 gene respectively. In chTLR3, 1 deleterious SNP was located in ectodomain and 3 were located in the Toll / IL-1 receptor (TIR) domain. Further structural model of chTLR3-TIR domain suggested that 1 deleterious SNP be present in the B-B loop region, which is important for TIR-TIR domain interactions in the downstream signaling. In chTLR4, the deleterious SNPs were located both in the ectodomain and TIR domain. SNPs predicted for chTLR3 and chTLR4 in this study, might be related to resistance or susceptible to viral infection in chickens. Results from this study will be useful to develop the effective measures in chicken against infectious diseases.

Keywords

References

  1. Adzhubei I, Jordan DM, Sunyaev SR 2013 Predicting functional effect of human missense mutations using PolyPhen 2. Current Protocols in Human Genetics 76(1):7.20.1-7.20.41. https://doi.org/10.1002/0471142905.hg0720s76
  2. Al-Qahtani A, Al-Ahdal M, Abdo A, Sanai F, Al-Anazi M, Khalaf N, Viswan NA, Al-Ashgar H, Al-Humaidan H, Al-Suwayeh R 2012 Toll-like receptor 3 polymorphism and its association with hepatitis B virus infection in Saudi Arabian patients. Journal of Medical Virology 84(9):1353-1359. https://doi.org/10.1002/jmv.23271
  3. Botos I, Segal DM, Davies DR 2011 The structural biology of Toll-like receptors. Structure 19(4):447-459. https://doi.org/10.1016/j.str.2011.02.004
  4. Cheng J, Sun Y, Zhang X, Zhang F, Zhang S, Yu S, Qiu X, Tan L, Song C, Gao S 2014 Toll-like receptor 3 inhibits Newcastle disease virus replication through activation of pro-inflammatory cytokines and the type-1 interferon pathway. Archives of Virology 159(11):2937-2948. https://doi.org/10.1007/s00705-014-2148-6
  5. Iwasaki A, Medzhitov R 2015 Control of adaptive immunity by the innate immune system. Nature Immunology 16(4):343. https://doi.org/10.1038/ni.3123
  6. Kalaiyarasu S, Bhatia S, Mishra N, Sood R, Kumar M, SenthilKumar D, Bhat S, Prakash MD 2016 Elevated level of pro inflammatory cytokine and chemokine expression in chicken bone marrow and monocyte derived dendritic cells following LPS induced maturation. Cytokine 85:140-147. https://doi.org/10.1016/j.cyto.2016.06.022
  7. Kruglyak L, Nickerson DA 2001 Variation is the spice of life. Nature Genetics 27(3):234. https://doi.org/10.1038/85776
  8. Lee SO, Brown R, Razonable RR 2013 Association between a functional polymorphism in Toll-like receptor 3 and chronic hepatitis C in liver transplant recipients. Transplant Infectious Disease 15(2):111-119. https://doi.org/10.1111/tid.12033
  9. Leveque G, Forgetta V, Morroll S, Smith AL, Bumstead N, Barrow P, Loredo-Osti J, Morgan K, Malo D 2003 Allelic variation in TLR4 is linked to susceptibility to Salmonella enterica serovar Typhimurium infection in chickens. Infection and Immunity 71(3):1116-1124. https://doi.org/10.1128/IAI.71.3.1116-1124.2003
  10. Medzhitov R 2001 Toll-like receptors and innate immunity. Nature Reviews Immunology 1(2):135. https://doi.org/10.1038/35100529
  11. Ng PC, Henikoff S 2003 SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Research 31(13):3812-3814. https://doi.org/10.1093/nar/gkg509
  12. O'neill LA, Golenbock D, Bowie AG 2013 The history of Toll-like receptors-redefining innate immunity. Nature Reviews Immunology 13(6):453. https://doi.org/10.1038/nri3446
  13. Paul MS, Brisbin JT, Abdul-Careem MF, Sharif S 2013 Immunostimulatory properties of Toll-like receptor ligands in chickens. Veterinary Immunology and Immunopathology 152(3-4):191-199. https://doi.org/10.1016/j.vetimm.2012.10.013
  14. Philbin VJ, Iqbal M, Boyd Y, Goodchild MJ, Beal RK, Bumstead N, Young J, Smith AL 2005 Identification and characterization of a functional, alternatively spliced Toll-like receptor 7 (TLR7) and genomic disruption of TLR8 in chickens. Immunology 114(4):507-521. https://doi.org/10.1111/j.1365-2567.2005.02125.x
  15. Rahim A, Kumar S, Debnath J, Yadav R, Das AK, Yadav A 2017 Fold changes in relative mRNA expression of immune response genes in lymphoid tissues of Rhode Island Red chicken. Indian Journal of Animal Sciences 87(6):108-110.
  16. Ruan W, An J, Wu Y 2015 Polymorphisms of chicken TLR3 and 7 in different breeds. PloS one 10(3):e0119967. https://doi.org/10.1371/journal.pone.0119967
  17. Ruan W, Wu Y, An J, Zheng S 2012 Polymorphisms of chicken Toll-like receptors 4, 15, and 21 in different breeds. Poultry Science 91(10):2512-2516. https://doi.org/10.3382/ps.2012-02319
  18. Shastry BS 2009 SNPs: Impact on gene function and phenotype. Single Nucleotide Polymorphisms 578:3-22.
  19. St. Paul M, Barjesteh N, Brisbin JT, Villaneueva AI, Read LR, Hodgins D, Nagy E, Sharif S 2014a Effects of ligands for Toll-like receptors 3, 4, and 21 as adjuvants on the immunogenicity of an avian influenza vaccine in chickens. Viral Immunology 27(4):167-173. https://doi.org/10.1089/vim.2013.0124
  20. St. Paul M, Brisbin JT, Barjesteh N, Villaneueva AI, Parvizi P, Read LR, Nagy E, Sharif S 2014b Avian influenza virus vaccines containing Toll-like receptors 2 and 5 ligand adjuvants promote protective immune responses in chickens. Viral Immunology 27(4):160-166. https://doi.org/10.1089/vim.2013.0129
  21. Stewart CR, Bagnaud-Baule A, Karpala AJ, Lowther S, Mohr PG, Wise TG, Lowenthal JW, Bean AG 2012 Toll-like receptor 7 ligands inhibit influenza A infection in chickens. Journal of Interferon & Cytokine Research 32(1):46-51. https://doi.org/10.1089/jir.2011.0036
  22. Wang D, Sadee W 2006 Searching for polymorphisms that affect gene expression and mRNA processing: Example ABCB1 (MDR1). The AAPS Journal 8(3):E515-E520. https://doi.org/10.1208/aapsj080361
  23. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T 2018 SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res 46(W1):W296-W303. https://doi.org/10.1093/nar/gky427