Association of toll-like receptor polymorphisms with susceptibility to chikungunya virus infection

Virology. 2017 Nov:511:207-213. doi: 10.1016/j.virol.2017.08.009. Epub 2017 Sep 6.

Abstract

Chikungunya virus (CHIKV) infection leads to activation of innate immune response by triggering Toll-like receptor (TLR) pathways resulting in elevated cytokines and type-I interferon levels. Genetic variations of these genes may influence human CHIKV-susceptibility and disease progression. Present study aimed to identify role of TLR polymorphisms in CHIKV-susceptibility and their association with cytokines and clinical symptoms. This is the first study illustrating certain genotypes of TLR-7 and TLR-8 SNPs viz. CT(p = 0.002)]; rs3853839[GC(p < 0.001), CC(p = 0.039)] and rs3764879[GC(p < 0.001)] were considerably associated with CHIKV susceptibility. Increased risk of CHIKV infection among male patients with CC-genotype (rs179010) (p = 0.028) and female patients with GT-genotype (rs5741880) (p = 0.019) was observed. Significant higher IFN-α (P = 0.002) levels among chikungunya TNF-α (P = 0.034) patients was reported. Chikungunya patients with rs179010-CC genotype showed significantly high IFN-α level(p = 0.003). Thus, these TLR variants might act as potential prognostic biomarkers for predicting CHIKV susceptibility among uninfected individuals.

Keywords: Chikungunya; IFN-α; IL-6; MYD88; OAS3; Single nucleotide polymorphism (SNP), Symptoms; TLR-3; TLR-7; TLR-8; TNF-α.

MeSH terms

  • Chikungunya Fever / genetics*
  • Chikungunya Fever / immunology
  • Chikungunya Fever / pathology
  • Cytokines / metabolism
  • Genetic Predisposition to Disease*
  • Humans
  • Polymorphism, Single Nucleotide*
  • Toll-Like Receptor 7 / genetics*
  • Toll-Like Receptor 8 / genetics*

Substances

  • Cytokines
  • TLR7 protein, human
  • TLR8 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8