A functional Toll-like receptor 3 gene (TLR3) may be a risk factor for tick-borne encephalitis virus (TBEV) infection.

Tick-borne encephalitis virus (TBEV) infections may be asymptomatic or cause severe symptoms in the central nervous system. A mutation in the chemokine receptor 5 gene has been associated with increased risk of TBE but explains only a limited number of cases. Investigations of further risk factors are needed. To investigate the importance of the innate immune response, we analyzed 128 TBE patients, 77 patients with aseptic meningoencephalitis (AME) and 135 healthy controls, for 3 mutations: 2 in the Toll-like receptor 3 (TLR3) gene and 1 in the 2'-5'-oligoadenylate synthetase (OAS1) gene. Although no association was found between the mutation in the OAS1 gene and TBE, the genotype distribution ofrs3775291, a mutation in TLR3, differed significantly between TBE patients and controls; 61%, 32%, and 7% of the TBE patients were carriers of the wild-type, heterozygous, and mutant genotype of rs3775291, respectively. The corresponding percentages among healthy controls (n = 126) were 52%, 29%, and 19% (P = .02), and among AME patients (n = 75) were 47%, 32%, and 21% (P = .009). Additionally, the wild-type rs3775291 allele was more common among TBE patients than among healthy controls (allele frequency, .768 vs .663; P = .01). A functional TLR3 is a risk factor for TBEV infection.