Imagine a world where a single gene discovery could revolutionize the way we treat viral infections and immune disorders. That’s exactly what researchers at the University of Kansas have stumbled upon, and it’s a game-changer. In a groundbreaking study published in the journal mBio (https://journals.asm.org/doi/10.1128/mbio.02299-25), scientists have uncovered the role of a human gene encoding the protein PARP14 in regulating interferon, a key player in our body’s innate immune system. But here’s where it gets even more fascinating: this protein doesn’t just fight viruses—it does so in multiple ways, boosting the immune response while directly targeting viral invaders.
Led by senior author Anthony Fehr, an associate professor of molecular biosciences, the team initially focused on coronaviruses, particularly during the intense research efforts surrounding COVID-19. And this is the part most people miss: PARP14, found in humans and all mammals, exhibits antiviral activity against not just one, but multiple viruses. “It’s like discovering a Swiss Army knife in our genetic toolkit,” Fehr explains. “The human body is constantly in an arms race with viruses, and PARP14 is one of our most versatile weapons.”
But the story doesn’t end there. Collaborating with KU professor David Davido, the team found that PARP14 also targets HSV-1, the virus responsible for herpes simplex. This dual functionality has earned them a new grant to explore its role in herpes viruses, alongside their ongoing coronavirus research. Yet, here’s the controversial twist: while PARP14 fights some viruses, it actually enhances the replication of others, like rhabdoviruses, which include the rabies virus. This dual nature raises bold questions: Could PARP14 be both a hero and a villain in the viral world?
Fehr believes this complexity opens up a world of possibilities. “Understanding how PARP14 works could lead to new antiviral therapies for everything from COVID-19 to rabies,” he says. But the implications go even further. Since PARP14 plays a critical role in boosting innate immunity, it could also be a target for treating inflammatory diseases like autoimmunity and diabetes. Overactive immune responses often trigger these conditions, and inhibiting PARP14 might offer a way to temper them.
This discovery has already sparked exciting collaborations within KU’s medical research community. Fehr is now working with Hubert Tse, chair of microbiology at KUMC, to explore PARP14’s potential role in diabetes. “This protein’s impact on the immune response is so broad that it could reshape how we approach nonviral diseases,” Fehr notes.
The study, funded by the National Institute of General Medical Sciences and supported by KU’s Chemical Biology of Infectious Disease COBRE program, involved a multidisciplinary team of researchers from KU, Oregon Health & Science University, the University of Texas at Austin, Boston University, Harvard Medical School, and Brigham and Women’s Hospital. Their collective efforts highlight the power of collaboration in unlocking the secrets of our genetic code.
But here’s the question that lingers: As we uncover more about PARP14’s dual role in viral infections, how should we balance its potential as a therapeutic target with its ability to promote certain viruses? Is it a risk worth taking, or should we proceed with caution? Share your thoughts in the comments—this discovery is just the beginning of a much larger conversation.
