Transmission and modulation of Powassan virus pathogenesis by ticks

The zoonotic tick-borne encephalitis is increasing in Sweden.

In North America the close relative Powassan virus (POWV) is increasing with the aggressive tick vector Ixodes scapularis. There is no vaccine or treatment for POWV.

To develop and test treatments against emerging zoonotic tick-borne viruses there is a need to fully understand the mechanisms of pathogenesis.

One important feature of these tick–borne viruses is that during transmission the tick feeds on the vertebrate for days, secreting factors in the saliva that affect infection and immune cells. Our hypothesis is that tick feeding influences pathogenicity.

We will use novel techniques to study POWV pathogenesis, comparing the local response in the skin following intradermal injection of virus or infection via tick feeding using single cell RNA sequencing. This will give a road map of the events leading to viremia and spread to the central nervous system.

In our second aim we will follow virus infection over time to identify the mechanism of neuroinvasion and tropism in the brain. We will use state of the art imaging to visualize virus infection in whole cleared brains over time.

Lastly, we will characterize the cellular response in infected brain regions at different time points using our recently developed protocol for single nuclei RNA sequencing.

This proposal will determine how long-term tick-feeding affects infection, neuroinvasion, tissue tropism and cellular response in the brain.