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Background  Tick-borne encephalitis virus (TBEV) infections can be asymptomatic or cause moderate to severe injuries of the nervous system. We previously reported that a nonfunctional chemokine receptor 5 (CCR5) and a functional Toll-like receptor 3 (TLR3) predispose adults to clinical tick-borne encephalitis (TBE). This study expands our previous findings and further examines polymorphisms in  CCR5  and  TLR3  genes in different age and disease severity groups.    Methods  117 children and 129 adults, stratified into mild, moderate and severe forms of TBE, and 103 adults with severe TBE were analyzed. 135 healthy individuals and 79 patients with aseptic meningoencephalitis served as controls.  CCR5 delta 32  and rs3775291  TLR3  genotypes were established by pyrosequencing, and their frequencies were analyzed using recessive genetic, genotype and allelic models.    Findings  The prevalence of  CCR5Δ32  homozygotes was higher in children (2.5%), in adults with severe TBE (1.9%), and in the combined cohort of TBE patients (2.3%) than in controls (0%) (p<0.05). The nonfunctional homozygous  TLR3  genotype was less prevalent among the combined TBE cohort (11.5%) than among controls (19.9%) (p = 0.025), but did not differ between children TBE and controls. The genotype and allele prevalence of  CCR5  and  TLR3  did not differ in children nor adult TBE cohorts stratified by disease severity. However, in the severe adult TBE cohort, homozygous functional  TLR3  genotype and wt allele were less prevalent compared to the adult cohort with the whole disease severity spectrum (44.4% vs 59.8% p = 0.022 and 65.2% vs 76.4% p = 0.009; respectively).    Conclusions  Independently of age, nonfunctional  CCR5Δ32  mutation is a significant risk factor for development of clinical TBE, but not for disease severity. The polymorphism of  TLR3  gene predisposes to clinical TBE in adults only and may be associated with disease severity. Further studies are needed to clarify the role of these polymorphisms in susceptibility to TBEV infection.

plos one

Polymorphisms in Chemokine Receptor 5 and Toll-Like Receptor 3 Genes Are Risk Factors for Clinical Tick-Borne Encephalitis in the Lithuanian Population