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.

ISG expression varies based on cell and tissue type. Therefore, we set out to define ISGs in Calu3 cells, a human respiratory cell line permissive for both CoV and influenza infection. Calu3 cells were treated with type I IFN (IFN-␣ or IFN-␤), resulting in differential expression of Ͼ350 genes (log 2 fold change [FC] of Ͼ1.5, adjusted P value of Ͻ0.05; Fig. 1A ). Using these data, a consensus ISG list was developed from genes induced at more than one time point (see Table S1 in the supplemental material) and then used to examine ISG expression changes following infection. While cytopathic effect (CPE) in both H5N1-VN1203 and H1N1-09 required a slightly lower multiplicity of infection (MOI) to maximize comparable time points, infection of the cultures was uniform (Ͼ95% infection), as measured by CPE or fluorescent virus infection. In addition, each infection maintained similar kinetics in terms of both replication and genomic RNA production despite differing endpoint titers ( Fig. 1B and C) .