||Studies on the virulence factor involved in the pathogenicity in tick-borne encephalitis virus infection
Tick-borne encephalitis virus (TBEV) is maintained among ticks and mammals in nature, and human can be infected with tick bite. Although about 10,000 cases have been reported annually in European countries and Russia, there is no attenuated live vaccine and anti-viral therapy. The virulence of TBEV varies among the strains. However, the mechanism of the viral pathogenicity is unknown. To clarify the mechanism, I tried to identify the virulence factors by reverse genetics, using two different virulence viruses of the Far-Eastern subtype of TBEV; a highly pathogenic strain Sofjin-HO and a low pathogenic strain Oshima 5-10. I found that the variable region of the 3’-UTR is a critical virulence factor and the deletion in the variable region affected the different virulence in mice. Partial deletions or addition of polyA sequence in this region of Oshima also increased the virulence to the same level with Sofjin, although they did not affect the viral multiplication in mice brain and cultured cells. These mutations did not change the production of subgenomic flavivirus RNA from the 3’-UTR, and the induction of interferon (IFN) and IFN-stimulated genes. These data suggested that the whole conformational structure of the variable region is associated with the pathogenicity of the Far-Eastern subtype of TBEV by unknown mechanisms. These findings encourage further research to identify the pathogenic mechanisms of TBEV and develop prevention and therapeutic strategies for TBE.
Hokkaido University（北海道大学）. 博士(獣医学)