Functional RNA sequence elements in the TBE virus genome

Flaviviruses comprise a number of important human pathogens of world-wide medical importance. These viruses are usually transmitted to their vertebrate hosts by arthropod vectors, i.e. mosquitoes or ticks. Prominent members of the mosquito-bome group are yellow fever virus, Japanese encephalitis virus, the four serotypes of dengue virus, and West Nile virus, whereas the medically most important representative of the tick-bome flaviviruses is tick- bome encephalitis virus (TBEV) which is endemic in parts of Europe and Asia. The specificity of a virus for its transmission vector determines to a large extent the viral life cycle and thus the epidemiology and impact of the disease an human health. The molecular determinants that underlie the host specificity of flaviviruses are currently unresolved. The flavivirus genome, a positive-stranded RNA molecule, has at its ends short non-coding sequence elements that contain structural elements of presumed functional importance that are likely to be such determinants of host specificity. This project aims to identify and characterize specific sequence elements an the RNA genome of TBEV that control replication and translation of this virus. Sequence comparisons suggest that mosquito-bome and tick- bome flaviviruses, although sharing a very close molecular relationship in many respects, exhibit major differences with respect to putative functional RNA elements. Whereas experimental evidence for some of these control elements has been obtained for mosquito-bome flaviviruses, direct evidence is completely lacking in the case of tick-bome flaviviruses. The project leader and his group have developed during the past years genetic tools and techniques that will now be used to identify such elements for TBEV. The results of this study are expected to yield fundamental insights into regulatory processes of TBEV and to demonstrate differences between tick-bome and mosquito-bome flaviviruses that may form the basis of their different host specificities. Moreover, the characterization of TBEV control elements will be instrumental for the further development of TBEV-based gene expression vectors and vaccines.