Elucidating the mechanisms by which mosquito-borne viruses disseminate in vivo and cause disease

This project will determine the cellular basis by which arthropod-borne viruses (arboviruses) disseminate in vivo; a process that is essential for their transmission and pathogenesis. Arboviruses spread disease in humans and livestock. After infection by an arthropod bite, arboviruses disseminate to the blood (viraemia). Subsequently, arboviruses spread to distal sites where they can cause severe disease including encephalitis, arthritis or hemorrhagic fevers, the severity of which depends on the establishment of high viraemia. Importantly, little is known about which cell types fuel this viraemia and how arboviruses spread to distal sites.

This project will determine the origin of viraemia using an innovative technique based on inhibition of virus replication in specific cell types. By genetically engineering viruses to encode a microRNA target site in their genome, viral replication will be blocked specifically in cells expressing the corresponding microRNA. This will enable us to dissect the contribution of viral replication in defined cell compartments from the inoculation site to distal tissue, and so define the critical events that lead to systemic spread.

This will provide novel, fundamental insights that will aid the design of innovative treatment strategies.