Targeting Alimentary Systems in TBEV Experimentation

ongoing

Tick-borne encephalitis virus (TBEV) has an estimated mortality rate of up to 40%, and although transmission is primarily associated with tick bites, a secondary route is that of alimentary transmission. Alimentary transmission occurs through the ingestion of contaminated ‘raw’ dairy products. Since its discovery in the early 1950’s the incidence of TBEV due to this infection method has continuously increased, currently accounting for ~1% of all TBEV cases. Despite this, the alimentary route of infection is severely understudied, and there are no defined mechanisms by which TBEV breaches the intestinal epithelial barrier and disseminates to secondary tissues. To address this gap in knowledge, the TASTE (Targeting Alimentary Systems in TBEV Experimentation) project aims to elucidate the key molecular interactions (both extra- and intracellular) and examine these factors in a cellular and tissue context to establish a model for TBEV alimentary infection. A novel crosslinking immunoprecipitation pipeline will be developed, utilising the incorporation of photosensitive unnatural amino acids into the TBEV genome, to identify the host receptors responsible for virus binding and internalisation. RNA interactome capture and immunoprecipitation will be used to isolate the intracellular factors responsible for viral replication. Following this, the importance of these components and the influence of additional environmental factors will be examined in both cell culture and tissue models. The output of this project will not only be informative to the mechanisms of alimentary infection but will serve as a foundation for future research into therapeutics and patient treatment. I chose to pursue this project within the Ruzek lab at MUNI, as this lab excels in TBEV research and has all the resources necessary to achieve this work. By adding my expertise in molecular virology, we aim to develop novel angles in TBEV research from which future projects can be developed.