Powassan virus, a cousin to Zika and Dengue in the flavivirus family, is a rare tick-borne infection that is becoming more widespread in the northern U.S. Powassan symptoms include fever, nausea, and headaches. In severe cases, it can lead to brain swelling and potentially be fatal. Given how dangerous this virus is, it can only be studied in special, high-security labs.
A multidisciplinary team led by Susan Hafenstein, a professor in the University of Minnesota’s College of Biological Sciences, with graduate student and lead author Sayan Das, set out to study the Powassan virus under safer conditions. The team included members from the Huck Institutes of the Life Sciences at the Pennsylvania State University and the U.S. Department of Agriculture.
For new research published in Science Advances, the team tackled the problem by hacking the virus, swapping parts of it with a yellow fever virus vaccine strain, which is much safer to handle. Then they examined the doppelgänger (also known as a chimeric virus) in detail.
The team discovered:
- Using electron cryo microscopy on a frozen copy of the chimeric virus, the team was able to visualize the virus at the atomic level for the first time.
- They observed three hidden lipid pockets inside of the virus, one of which has a long, finger-like appearance that stretches to the viral core.
- When they mutated a single amino acid residue (Trp467) interacting with this pocket, the virus fell apart and could not reassemble, revealing an Achilles heel that could be used to develop vaccines and treatments.
“Basically, we made a lookalike version of Powassan virus — one that walks like Powassan and talks like Powassan, but is safe to handle in less secure labs,” said lead author and doctoral student Sayan Das. “Think of it like building a movie prop of a dangerous animal where you get the full appearance and behavior of the animal, but without the bite.”
Future research is likely to focus on the Trp467 amino acid, which triggered the collapse of the virus. Das compared it to pulling the wrong block in a game of Jenga. “This amino acid is present in most flaviviruses, which indicates that the virus falling apart because of the mutation might not just be a Powassan thing — it could be a universal vulnerability across flaviviruses. And this pressure point might be a target for future lipid-based antivirals.”