Newly Discovered Component of Interferon Signaling Pathway (PARP9-DTX3L Complex) Interacts with STAT1 and Also Has E3 Ubiquitin Ligase Activity to Both Boost Interferon-Stimulated Gene Expression & Degrade Viral 3C Proteases with One-Two Punch

Many viral infections, such as the common cold, cause mild illnesses that the body's immune system eventually defeats. But when viruses cause severe disease, doctors have few options for effective treatment. Studying mice with a variety of viral infections, scientists at the Washington University School of Medicine in St. Louis (WUSL School of Medicine) have demonstrated a way to dial up the body's innate immune defenses, while simultaneously attacking a protein that many viruses rely on to replicate. The findings, published online on October 19, 2015 in Nature Immunology, reveal previously unknown weapons in the body's antiviral immune arsenal and provide guidelines for designing drugs that could be effective against a broad range of viruses. The new article is titled “PARP9-DTX3L Ubiquitin Ligase Targets Host Histone H2BJ and Viral 3C Protease to Enhance Interferon Signaling and Control Viral Infection.” The strategy involves enhancing the body's interferon signaling system, long understood to be a vital part of antiviral defenses. "We've discovered a new component of the interferon system," said senior author Michael J. Holtzman, M.D., the Selma and Herman Seldin Professor of Medicine. "It does something that other components don't do, and it works on both sides of the fence: It dials up the body's internal genes that fight viruses, and it attacks viral proteins directly." Dr. Holtzman and lead author Yong Zhang, Ph.D., an Instructor in Pulmonary Medicine WUSL School of Medicine, suspect that this one-two punch against the virus may explain the large difference in survival rates between control mice and mice genetically engineered to have increased signaling in their interferon systems.
Login Or Register To Read Full Story