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.

Locus. We next sought to determine whether down-regulation of antigen presentation was limited to IFN-γ-responsive genes or could be detected across the entire spectrum of antigen-presentation molecules. Therefore, we next examined gene expression of both MHC molecules and other components associated with antigen presentation; the majority of these genes were located within the MHC locus on human chromosome 6 (chr. 6), while others were interspersed throughout the genome (Table S2 ). The results indicated broad down-regulation of antigen-presentation molecules following both H5N1-VN1203 and MERS-CoV infection (Fig. 2 ). In contrast, H1N1-09 infection had no effect or strongly increased expression of these genes; similarly, SARS-CoV also induced expression for the majority of these genes. Globally, both H5N1-VN1203 and MERS-CoV infection resulted in reduced expression of both MHC class I and II molecules. Similarly, the expression of other genes involved in antigen presentation, including transcription factors (CTIIA) and machinery (TAP2 and PDIA3), both in the MHC locus and on other chromosomes (distant), was also strongly down-regulated. Importantly, while adjacent genes on chr. 6 not involved in antigen presentation and MHC class III genes (complement, TNF, etc.) had some modulation, down-regulation was not uniform, suggesting specific targeting of MHC and antigenpresentation molecules by both H5N1-VN1203 and MERS-CoV.