Human Protein PARP14 Found To Fight Multiple Viruses

Researchers at the University of Kansas have discovered a human gene, the protein PARP14, plays a role in regulating interferon, part of the body’s innate immune system. Their study, appearing in journal mBio, could guide development of antiviral therapies for several groups of viral infection.

“We found for the first time that PARP14, a gene encoded by humans and all mammals, had antiviral activity against multiple viruses,” said senior author Anthony Fehr, associate professor of molecular biosciences at the University of Kansas, who led the research. “It also helps boost the immune response, which demonstrates that this protein is fighting viral infections in multiple ways.”

The KU researcher said the protein, PARP14, was a discovery born of the intense research effort in Fehr’s lab to help characterize and fight COVID-19.

“We primarily work with coronaviruses, so that was the first virus where we discovered antiviral activity of PARP14,” Fehr said. “The human body devotes enormous resources to antiviral defense, and the virus is always trying to evade those defenses. It’s an arms race — a back-and-forth between host and virus. PARP14 is one of the host’s tools to kill viruses, and the virus evolves ways to escape. These discoveries can lead to new insights into how to treat innate immune disorders or viral infections.”

Later, working with KU professor of molecular biosciences David Davido, Fehr found PARP14 also targets HSV-1, or herpes simplex virus. “So, we’ve just received a new grant to study PARP14’s role in herpes viruses, in addition to continuing our coronavirus research,” he said.

While PARP14 shows promise for antiviral activity, the protein also can promote certain viruses. Such interactions will be the basis for future study, according to Fehr, with the goal of honing effective drug therapies for humans and animals, potentially spanning different groups of viruses including COVID-19.

“We found PARP14 has what we call ‘proviral activity’ — it enhances the replication of another class of viruses called rhabdoviruses, like rabies virus,” he said. “That indicates there could be a lot of potential translational opportunities with this protein. It could be a target for antivirals for rabies-like viruses, since it’s important for these viruses, and further understanding of how it works could also lead to better antivirals for COVID, coronaviruses or herpes viruses.”

Past that, PARP14 could even show promise for pharmaceutical research aimed at nonviral ailments.

“The big picture for us is its effect on the innate immune response,” Fehr said. “Knowing that this protein is important for boosting innate immunity could affect many diseases related to inflammation. Autoimmunity and diabetes, for instance, can be triggered by overactive immune responses. By inhibiting PARP14, it might be possible to temper or reduce these conditions.”

Indeed, Fehr said the promise of PARP14 has led to new collaborations within KU’s medical-research community.

“This idea is really exciting because it might let my lab eventually expand beyond viruses and work on other diseases,” he said. “I’m currently talking with the chair of microbiology at KUMC, Hubert Tse, who does diabetes research. His group recently found a link between innate immune response and diabetes, and we’re interested to see if PARP14 might play a role.

“Whenever you have a protein that affects the general immune response, there are opportunities to target it for inflammatory diseases.”

Reference: Parthasarathy S, Saenjamsai P, Hao H, et al. PARP14 is an interferon-induced host factor that promotes IFN production and affects the replication of multiple viruses. mBio. 2025;16(10):e02299-25. doi: 10.1128/mbio.02299-25

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