Deciphering PARP14's Role in Viral Pathogenesis

Researchers at the University of Kansas have identified that the human gene encoding the protein PARP14 plays a crucial role in regulating interferon, a key component of the body’s innate immune system. The study, published in the journal mBio, could help advance the development of antiviral treatments targeting various groups of viral infections.

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*Important notice: mBio publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

We found for the first time that PARP14, a gene encoded by humans and all mammals, had antiviral activity against multiple viruses. It also helps boost the immune response, which demonstrates that this protein is fighting viral infections in multiple ways.

Anthony Fehr, Study Senior Author and Associate Professor, Molecular Biosciences, University of Kansas

The discovery of the protein PARP14 emerged from the research efforts in Fehr’s lab aimed at understanding and combating COVID-19.

“We primarily work with coronaviruses, so that was the first virus where we discovered antiviral activity of PARP14,” Fehr says.

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.

Anthony Fehr, Study Senior Author and Associate Professor, Molecular Biosciences, University of Kansas

In collaboration with David Davido, Fehr discovered that PARP14 also targets HSV-1, the 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.

Although PARP14 demonstrates potential antiviral activity, it can also enhance the replication of certain viruses. According to Fehr, these complex interactions will be the focus of future research aimed at developing effective drug therapies for humans and animals, potentially targeting a broad range 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 notes. “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.”

Beyond antiviral research, PARP14 may also hold potential for pharmaceutical studies targeting nonviral diseases.

“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.

Anthony Fehr, Study Senior Author and Associate Professor, Molecular Biosciences, University of Kansas

*Important notice: mBio publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.