Characterization and complete genome sequences of high- and low- virulence variants of tick-borne encephalitis virus

The entire genomic sequences of two strains (Hypr and 263) of the flavivirus tick-borne encephalitis (TBE) virus differing in virulence from the prototypic strain Neudoerfl were determined. Strain Hypr is a human isolate of TBE virus with a high laboratory passage history which exhibits a significantly higher neuro-invasiveness in mice compared to the prototype strain. Strain 263 is a low-passage tick-isolate with a temperature-sensitive and attenuated phenotype. Except for the heterogeneous 3' non-coding regions strains Hypr and 263 share, respectively, 97.2% and 97.6% nucleotide sequence identity with strain Neudoerfl, and differ by a total of 42 and 36 amino acids from the prototypic strain. Of these, only 12 amino acids for each of the two strains represent non-conservative differences unique to an individual strain and some of these are located at positions highly conserved among flaviviruses. Based on these observations, the potential biological significance of particular sequence differences is discussed in the context of the current knowledge about molecular determinants of flavivirus virulence.