Pathogenic Influenza Viruses and Coronaviruses Utilize Similar and Contrasting Approaches To Control Interferon-Stimulated Gene Responses

Menachery, Vineet D.; Eisfeld, Amie J.; Schäfer, Alexandra; Josset, Laurence; Sims, Amy C.; Proll, Sean; Fan, Shufang; Li, Chengjun; Neumann, Gabriele; Tilton, Susan C.; Chang, Jean; Gralinski, Lisa E.; Long, Casey; Green, Richard; Williams, Christopher M.; Weiss, Jeffrey; Matzke, Melissa M.; Webb-Robertson, Bobbie-Jo; Schepmoes, Athena A.; Shukla, Anil K.; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; Katze, Michael G.; Kawaoka, Yoshihiro; Baric, Ralph S.

Overall, this study combines a systems biology approach that integrates complex RNA and proteomics datasets across different virus infections with detailed molecular and cell biology validation approaches to identify novel patterns and mechanisms of virus-host interaction and innate immune regulation. While ISGs have been previously known to be an important factor during viral infection, global analysis has been limited by the lack of uniform platforms, infection conditions, and data collection methods. Establishing conditions that afford comparisons across systems virology datasets alleviated these problems and permitted analysis beyond a single treatment or infection condition. The resulting study revealed similarities and stark contrasts in terms of ISG induction between SARS-CoV, MERS-CoV, an HPAI virus, and a 2009 pandemic influenza virus strain, which likely contribute to differences in disease outcomes and may help our understanding of these infections. Importantly, discovery-based studies informed molecular approaches that identified a novel avenue of immune antagonism utilized by two diverse viral families, providing a new area for exploration and study. This study highlights the power and utility of combining systems biology and standard molecular-based approaches in emerging infectious disease research.