A protein that is critical in controlling replication of West Nile and Zika viruses -- and could be important for developing therapies to prevent and treat those viruses -- has been identified by a Georgia State University (GSU) biologist and his research group. The researchers found Z-DNA binding protein 1 (ZBP1) is a sensor that plays a significant role in triggering a robust immune response when it detects a viral infection within cells. The Georgia State study, published online on September 11, 2019 in the journal Frontiers in Microbiology, found that ZBP1 is essential for restricting both West Nile and Zika virus replication, and that it prevents West Nile-associated encephalitis (inflammation of the brain) in mice. The article is titled “"Z-DNA-Binding Protein 1 Is Critical for Controlling Virus Replication and Survival in West Nile Virus Encephalitis.” The absence of ZBP1 in mice leads to 100 percent mortality when mice are infected with even a non-disease-producing strain of West Nile Virus, the study found. "It's significant because you take a virus that has never been shown to kill anything and, if you block this protein, the virus will just kill everything," said Mukesh Kumar, PhD, Assistant Professor of Biology at GSU, and senior author of the study. "We discovered that when cells are infected with viruses such as Zika and West Nile, they respond by triggering necroptosis, a form of programmed cell death, via ZBP1 signaling. This inhibits viral replication and spread, allowing the immune system to clear the virus." Dr. Kumar said the findings could present new treatment strategies for viruses that can infect the central nervous system by modulating ZBP1 expression. Subsequent research by Dr. Kumar's team will explore effectiveness against similar viruses such as Eastern equine encephalitis and Powassan virus.
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