Kurhade et al.
Correlation of severity of human tick-borne encephalitis virus disease and pathogenicity in mice.
Emerg. Infect. Dis. 2018, in press; doi.org/10.3201/eid2409.171825
The pathogenicity of two TBE virus strains from different foci have been compared in C57BL/6 mice (subcutaneous challenge with 104 focus forming units). One strain -Torö-2003 – had caused 32 reported TBE cases during the period from 1986 to 2016 on the island of Torö in the Stockholm area, of which only four patients had relatively mild neurological disease. For comparison, strain MucAr HB171/11 had been isolated in southeastern Germany and had caused only mild gastrointestinal and constitutional symptoms without neurological symptoms (in five patients). Infection with Torö-2003 strains caused fatal outcome in all mice with a median survival time of 13 days, while after infection with HB171/11, only 60% of the mice died and the median survival time was 18.5 days. Compared to strain Torö, strain HB171/11 induced various cytokines in infected mice. When virus (100 focus forming units) was injected into the cerebral cortex of mice, strain Torö was highly pathogenic leading to 100% death, while the observed neurovirulence was lower when strain HB171/11 was injected. In total, the pathogenicity, neurovirulence, neuroinvasiveness and proinflammatory response in mice of these two strains clearly differed. These data are supportive to understand pathogenesis of TBE in humans.