MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape

Menachery, Vineet D.; Schäfer, Alexandra; Burnum-Johnson, Kristin E.; Mitchell, Hugh D.; Eisfeld, Amie J.; Walters, Kevin B.; Nicora, Carrie D.; Purvine, Samuel O.; Casey, Cameron P.; Monroe, Matthew E.; Weitz, Karl K.; Stratton, Kelly G.; Webb-Robertson, Bobbie-Jo M.; Gralinski, Lisa E.; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; Sims, Amy C.; Kawaoka, Yoshihiro; Baric, Ralph S.

Genes. In parallel to RNA expression analyses, antigen-presentation components were examined within the context of global proteomics. As expected, peptides associated with antigen-presentationrelated molecules were detected in baseline mock-infected proteomic samples. Consistent with transcriptomic data, peptides mapping to class I MHC proteins (HLA-A, -B, or -C) exhibited statistically significant decreases after MERS-CoV or H5N1-VN1203 infection, but were significantly increased in cells infected with SARS-CoV or H1N1-09 (Fig. 3) . Interestingly, while MERS-CoV infection strongly down-regulated HLA-A, -B, and -C peptides, H5N1-VN1203 infection consistently down-regulated HLA-A and -C, but not HLA-B, peptides (Fig. 3) . Peptides IFN-γ-responsive gene divided into functional categories and classified as either up-regulated (log2 FC > 0) or down-regulated (log2 FC < 0). Boldface, MHC and antigen presentation-related molecules had >80% downregulation in both H5N1-VN1203 and MERS-CoV (n = 15 genes). associated with other (non-HLA) antigen-presentation proteins exhibited similar overall expression patterns (Fig. 3A) . Together, the transcriptomic and proteomic data indicate that antigen-presentation molecule expression is antagonized by MERS-CoV and H5N1-VN1203 infections-with some potential differences in efficiency or mechanism of antagonism-but not by SARS-CoV and H1N1-09 infections.