Researchers at the University of Kansas have uncovered a human gene, PARP14, that could serve as a promising drug target for antiviral therapies and immune-related disorders. Published in the journal mBio, the study shows that this protein plays a key role in regulating the body’s innate immune system and may help combat a variety of viral infections.
The discovery, led by Anthony Fehr, associate professor of molecular biosciences at KU, reveals that PARP14 has antiviral activity against multiple viruses, including coronaviruses and herpes simplex virus (HSV-1). By enhancing the immune response while directly targeting viral replication, PARP14 operates on multiple fronts in the body’s defense against infections.
“Our research demonstrates that PARP14 is a human-encoded protein that fights viral infections while also supporting the immune system. Understanding its mechanisms could lead to new drug therapies for viral diseases and immune disorders,” Fehr said.
The protein was first investigated in the lab’s coronavirus studies during the COVID-19 pandemic. Researchers observed that PARP14 could limit viral replication while boosting interferon, a key component of the innate immune system. This “arms race” between host and virus, as Fehr describes it, reflects the ongoing struggle where the body deploys defenses like PARP14, and viruses evolve strategies to evade them.
Further experiments revealed that PARP14 also affects other viruses in surprising ways. While it inhibits some viruses, it can promote the replication of rhabdoviruses, including the rabies virus. This dual activity, referred to as “proviral activity,” suggests that PARP14 could be manipulated to either suppress or support viral growth, depending on therapeutic goals.
“This protein has potential for broad translational applications. It could become a drug target for antivirals against rabies-like viruses while also informing treatments for coronaviruses or herpes viruses,” Fehr noted.
Beyond its antiviral functions, PARP14 may influence immune-mediated diseases such as diabetes and autoimmune disorders. Because it modulates the innate immune response, targeting PARP14 could help manage overactive immune reactions that contribute to inflammation. KU researchers are exploring collaborations to investigate PARP14’s impact on conditions like diabetes, aiming to harness the protein for both viral and nonviral drug therapies.
The discovery has already prompted new research directions and grant support for continued study of PARP14. Fehr, working with KU professor David Davido and other collaborators, plans to further explore the protein’s role in viral infections and immune regulation. The ultimate goal is to develop therapies that can selectively enhance or inhibit PARP14’s activity, offering new drug-based treatment avenues for viral infections and immune-related conditions in humans and animals.
As researchers continue to unravel the complexities of PARP14, the findings highlight the importance of understanding the body’s innate defenses and their potential to inform innovative drug therapies. By targeting proteins like PARP14, scientists hope to create treatments that not only fight viruses more effectively but also regulate immune responses to prevent harmful inflammation, opening a path to safer and more precise interventions for a wide range of diseases.