Identification of viral RNA sequence determinants and viral/cellular proteins involved in regulation of flavivirus replication: implications for vaccine design

The main objective of my present research is to develop a vaccine against flavivirus infection. In order to accomplish that, it is imperative to first understand how the virus functions and exploits host cell machinery in order to complete its infectious cycle.

Mosquito-borne flaviviruses are serious pathogens associated with significant morbidity and mortality worldwide and there is no specific therapy for treatment of infection with any of the flaviviruses. The virus can cause severe CNS disease in humans, horses and other animals.

Flaviviruses are a viral family of RNA viruses. All RNAs in a cell are associated with proteins and RNAs are dependent on these interactions to function efficiently. Interactions of RNA with proteins depend on the RNA sequence and secondary structure. The exact RNA sequence is therefore of paramount importance since it affects secondary structure, function and utilisation efficiencies of the viral RNAs. West Nile Virus (WNV) contains an RNA genome, which is flanked by the 5’- and 3’- untranslated region (UTR) that play essential roles in viral gene regulation, initiation of translation, and RNA replication. Two regions of the virus are of special interest in my research: the UTR and the non-structural (NS) gene. My research aims to identify viral RNA sequence determinants and virus/host RNA-protein and protein-protein interactions involved in viral gene regulation and virus replication, using both bioinformatics and molecular biology approaches.

It is also highly likely that the knowledge obtained in the study on WNV infection will be transferable to other flavivirus infection, such as Japanese encephalitis (JE) virus, Dengue (DEN) virus, and Tick-borne encephalitis (TBE) virus.