Exploring an antiviral factor that helps, rather than hinders, influenza

By Meghan Chua


Mitch Ledwith is motivated every day by the excitement that comes with new, and sometimes unexpected, discoveries.

As a PhD student in Cellular and Molecular Biology and a research assistant in the Mehle lab, Ledwith has been a firsthand witness to just one of those exciting discoveries on the University of Wisconsin–Madison campus, through a project funded by a UW2020 grant.

The project seeks to identify host factors that regulate infections by viruses and other pathogens, then determine the molecular mechanisms of those regulators. A previous graduate research assistant in the lab designed a screen to find out what host factors viruses, such as influenza, use for their own benefit. The results were unexpected, Ledwith said.

Genomic approaches to identify host factors“What actually popped out as the factor that the flu likes to have around the most was an antiviral factor,” he said. “So how did this pro-viral factor – something that’s helping the virus – pop out when its usual function is to prevent viruses?”

Though antiviral factors normally fight pathogens, the flu virus uses that particular antiviral factor to boost its life cycle, Ledwith said.Ledwith uses computational sequencing to find out how the antiviral factor that the flu likes to have around still prevents other viral infections, and what it does when it comes in contact with influenza.

Understanding how viral and host factors regulate infection can inform development of antiviral therapies and drugs. Determining how the flu virus specifically can take advantage of an antiviral factor can further inform flu prevention efforts.

The lab’s discovery has earned additional funding for the project. Using preliminary data from the UW2020 project, Ledwith recently secured a 2018 National Science Foundation Graduate Research Fellowship that will fund the rest of his PhD career. Principal Investigator Andrew Mehle previously received a 2017 Burroughs Wellcome Fund grant based on the lab’s preliminary research in the project as well.

Ledwith said the UW2020 grant was instrumental in getting the lab’s research off the ground, since the lab has used a variety of specific techniques to address its questions.

“We’re using a very wide expanse of tools, and I think that a lot of this stuff has become available to us because we originally were funded through UW2020,” he said.

The next steps for the lab are to continue researching how viruses might use the family of proteins that includes the factor in question for their own gain. Viruses have to evolve in a specific cellular environment, usually an antiviral one.

“That’s the only environment they actually know,” Ledwith said. “If you think about it that way, then it makes sense that viruses are using some of these things that are just always around, because that’s just what’s available to them to use as tools to drive their own evolution and replication.”

The UW2020 initiative supports innovative and groundbreaking research at the University of Wisconsin–Madison with the potential to transform a field of study. UW2020 grants are supported by the Wisconsin Alumni Research Foundation (WARF) with combined funding from the Graduate School and other sources.