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.

The data also highlight the ability of both SARS-CoV and MERS-CoV to inhibit recognition, delay IFN induction, and sequester ISG production until after peak viral titers had been achieved. This ability effectively neutralizes the innate immune response and permits both CoVs to establish a foothold within the lung prior to recognition. However, MERS-CoV and SARS-CoV also utilize additional divergent approaches to limit the host IFN response. While SARS-CoV IFN antagonism is well established (11) , MERS-CoV appears to employ different, less effective antagonists, resulting in increased sensitivity to type I IFN pretreatment (15, 16) . However, altered histone modification represents a novel CoV antagonism approach. While newly emergent, several MERS-CoV proteins have been identified as IFN antagonists (50, 51) ; notably, ORF4b, a MERS accessory protein with no homologue in SARS-CoV, maintains a purported nuclear localization signal, exhibits nuclear localization based on transfection, and may play a role in IFN antagonism (51) . Further studies are under way utilizing the MERS-CoV infectious clone (52) and attempt to identify viral components required to mediate altered histone modification.