title: Test based on subtype-specific μ-capture IgM immunoassay can distinguish between infections of European and Siberian subtypes of tick-borne encephalitis virus.
abstract: BACKGROUND
  In many European countries (including Finland, Estonia, Latvia and Russia) two subtypes of tick-borne encephalitis virus (TBEV) occur with overlapping geographic distribution yet with apparently different severity and persistence of symptoms. However, it has not usually been possible to distinguish these infections in the laboratory, as TBEV RNA or sequences have rarely been retrieved from patients seeking medical care in the second phase of infection when the neurological symptoms occur, and serological tests have so far not been able to discriminate between the subtype-specific responses.
  
  
  OBJECTIVE
  The aim of this study was to assess the applicability of a μ-capture enzyme immunoassay (EIA) based on TBEV prME subviral particles produced in mammalian cells from Semliki-Forest virus replicons (SFV-prME EIA) to distinguish reactivity to European and Siberian strains of TBEV.
  
  
  METHODS
  Altogether 54 TBEV IgM positive acute human serum samples and 6 positive cerebrospinal fluid (CSF) samples from different regions of Finland were tested in EIA with subtype-specific antigens and TBEV-IgM subtype-specific index ratios were determined.
  
  
  RESULTS
  All 30 samples from patients whose transmission had occurred in foci where only Siberian subtype of TBEV is occurring had an index ratio of more than 1.8, whereas all 30 acute TBE samples from an area where only European subtype circulates had an index ratio below 1.5.
  
  
  CONCLUSIONS
  We conclude that the assay is a useful tool to distinguish between acute infections of European and Siberian strains of TBEV, and should help in further studies of the clinical outcome of these two subtypes.
authors.affiliation: Department of Virology, University of Helsinki, Helsinki, Finland. Electronic address: lev.levanov@helsinki.fi.
authors.forename: Lev
authors.initials: L
authors.lastname: Levanov
authors.affiliation: Department of Virology, University of Helsinki, Helsinki, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Jääskeläinen
authors.affiliation: Department of Virology, University of Helsinki, Helsinki, Finland; Department of Virology and Immunology, Helsinki University Hospital, Helsinki, Finland; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Vapalahti
mesh_terms: D003937:Diagnosis, Differential; D004669:Encephalitis Viruses, Tick-Borne / Q000145:classification* / Q000276:immunology; D004675:Encephalitis, Tick-Borne / Q000175:diagnosis* / Q000276:immunology*; D005060:Europe; D006801:Humans; D007118:Immunoassay; D007075:Immunoglobulin M / Q000097:blood / Q000134:cerebrospinal fluid; D007148:Immunoglobulin mu-Chains / Q000097:blood / Q000134:cerebrospinal fluid; D012800:Siberia
chemical_list: D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains
keywords: European subtype; Flaviviruses; Siberian subtype; TBEV subtype serodiagnostics; Tick-borne encephalitis virus