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.

This study demonstrates contrasting, similar, and novel avenues used by virulent respiratory viruses to dampen and impair the global ISG response. HPAI utilizes rapid manipulation resulting in both strong up-and downregulation of ISG subsets rather than a binary ISG response. In contrast, the less virulent H1N1-09 virus fails to modulate either ISG transcripts or protein, producing a robust antiviral state which may impact peak titers. Similarly, SARS-CoV infection stimulates robust ISG transcription and protein production; however, ISGs are delayed 24 to 48 h, permitting SARS-CoV to achieve peak titers prior to ISG production. Finally, MERS-CoV not only delays ISG induction but also manipulates a subset of ISGs, similar to H5N1-VN1203. Together, the data highlight methods that pathogenic viruses utilize to control the host antiviral state. In each case, the strategy contributes to successful infection and may explain differences in virulence seen between viral families and strains.