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John Schoggins (Milton E. Cassel Scholar) earned his B.S. in chemistry from the University of Rochester and his Ph.D. in molecular biology from the Weill Cornell Graduate School of Medical Sciences. He was a postdoctoral fellow in virology/infectious disease at The Rockefeller University, and has been on the faculty at UT Southwestern Medical Center in Dallas since 2012. In addition to being a Rita Allen Foundation Milton E. Cassel Scholar, he has been named a Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell, at UT Southwestern Medical Center and a Clayton Foundation Scholar. He has also received the Ruth L. Kirschstein National Research Service Award from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, the NIH New Innovator Award, and both the Sidney and Joan Pestka Award for Excellence in Interferon Research and the Seymour and Vivian Milstein Young Investigator Award from the International Cytokine and Interferon Society.

Interferons are among the first lines of defense against viral infection. The interferon-induced antiviral state is established by the transcription of hundreds of interferon-stimulated genes, many of which have direct antiviral effector functions. Previous screening efforts in Schoggins’ lab identified interferon alpha-inducible protein 6 (IFI6) as an inhibitor of yellow fever virus and dengue virus infection. His group has shown that IFI6 is inhibitory toward multiple flaviviruses, in some cases reducing viral titers 1,000-fold. Strikingly, this antiviral effect is highly specific, since the closely related hepatitis C virus is not inhibited. CRISPR-mediated deletion of IFI6 results in a strong attenuation of interferon sensitivity, suggesting that IFI6 plays a major role in the antiviral response during flavivirus infections. Using a variety of molecular virological and cell biological approaches, Schoggins’ team has shown that the mechanism of IFI6 action is inhibition of viral genome replication, but not earlier steps in the viral life cycle. They are currently addressing a potential role for flavivirus NS1 protein as a target of IFI6 action. In preliminary studies, ectopic expression of NS1 was able to rescue viral infection from the inhibitory effects of IFI6. These findings uncover a novel interferon-stimulated gene that potently and selectively inhibits replication of several important disease-causing flaviviruses.