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.

While previous studies have undertaken global analysis built on systems biology datasets (5) (6) (7) (8) , we took a new approach that focused on a parameter known to be important to viral infection: the interferon (IFN)-stimulated gene (ISG) response. Type I IFN induces a signaling cascade that provides the first line of defense against viral pathogens and initiates transcription of hundreds of ISGs that have antiviral, immune modulatory, and cell regulatory functions (9) . Successful viral pathogens, including CoVs and influenza viruses, have evolved genetic functions that antagonize pathogen recognition as well as ISG effector functions (10, 11) . Yet, as a whole, the ISG response has never been globally examined in the context of multiple viral pathogens in the same system; therefore, we sought to compare and contrast ISG control strategies employed by influenza A and pathogenic CoVs.