title: A functional Toll-like receptor 3 gene (TLR3) may be a risk factor for tick-borne encephalitis virus (TBEV) infection.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  A functional TLR3 is a risk factor for TBEV infection.
authors.affiliation: Division of Molecular Virology, Medical Faculty, University of Linköping, Linköping, Sweden. elin.kindberg@gmail.com
authors.forename: Elin
authors.initials: E
authors.lastname: Kindberg
authors.forename: Sirkka
authors.initials: S
authors.lastname: Vene
authors.forename: Aukse
authors.initials: A
authors.lastname: Mickiene
authors.forename: Åke
authors.initials: Å
authors.lastname: Lundkvist
authors.forename: Lars
authors.initials: L
authors.lastname: Lindquist
authors.forename: Lennart
authors.initials: L
authors.lastname: Svensson
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D004198:Disease Susceptibility; D004669:Encephalitis Viruses, Tick-Borne / Q000276:immunology*; D004675:Encephalitis, Tick-Borne / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D012307:Risk Factors; D051196:Toll-Like Receptor 3 / Q000235:genetics* / Q000276:immunology*
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase