Stiftelsen för forskning inom områden med anknytning till Östersjöregionen och Östeuropa

Molecular epidemiology, molecular evolution and vaccine development of Tick-borne encephalitis virus within the Baltic Sea region

Ämne: Biokemi, molekylärbiologi, miljövetenskap
Projektledare: Magnus Johansson
Startår: 2011
Projekttyp: Projekt

Tick-Borne Encephalitis virus (TBEV) cause severe CNS disease. Several factors, including climatechanges, have affected the TBEV distribution with significant outcome on the risks for human infections in the Baltic Sea region.
TBEV can be subdivided into three subtypes, Western European (W-), Sibirian- (S-) and Far Eastern-
(FE-) TBEV. The Baltic Sea region is an important study area as all three subtypes are present. Little is known about the molecular epidemiology of TBEV in Poland. As all the viral subtypes are co-circulating in the three Baltic States we believe that more virulent strains (S- and FE-) are present in northeast part of Poland, which calls for more profound TBEV studies within the region. Until recently, only W-TBEV has been detected in the Nordic countries, interestingly a recent report showed that the S-TBEV is abundantly present at the northern focus of Kokkola Finland. As e.g. birds can transport ticks over the Baltic Sea we hypothesise that S-TBEV could also be present at the corresponding Swedish latitude e.g. the Umeå area. This project will explore novel TBEV foci in northeast Sweden and northeast Poland with emphasis of the putative presence of S- and FE- TBEV.
In addition, it was recently proposed that diversity in TBEV virulence is due to the presence of viral
quasi-species within the tick reservoir. We have cloned a complete W-TBEV genome from ticks
collected in the Baltic-Sea region. This will be used to construct a TBEV infectious cDNA clone. The
clone would provide an intact virus free of ”quasi-species”. Studies on the virus evolution will be
performed by passaging this virus in three different ways; strictly through tick cells, mammalian cells or alternating between the two cell types. Sequences from evolved viruses will give important data on
essential genomic parts for respective host. The outcome will acquire knowledge on genetics, viral
evolution and molecular mechanism underlaying the TBEV pathogenesis.

Our recent work on molecular immune response to TBEV particularly viral protein NS5, will be used to
introduce mutations in an infectious cDNA clone creating putative novel TBEV vaccine candidates. In
addition, we are currently developing putative TBEV vaccine candidates based on the structural proteins expressed in plants in collaboration with Örebro University and Smittskyddsinstitutet. Improved TBEV vaccines will have great impact on future prevention strategies against TBEV in the Baltic-Sea region.