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.

To expand on this these findings for high-pathogenicity viruses (H5N1-VN1203 and MERS-CoV), we next performed ChIPsequencing (ChIP-seq) analysis for H3K4me3 and H3K27me3 and identified histone modification patterns for all genes on chr. 6, which contains the MHC locus. In H5N1-VN1203 infections, we observed depletion of H3K4 trimethylation across the length of chr. 6, with the strongest depletion in parts of the MHC locus (Fig. 4C) . Concurrently, few chr. 6 genes exhibited substantial depletion of H3K27 trimethylation (Fig. S1A) , and some were enriched for H3K27me3 (Fig. S1B ). Taken together, these observations suggest that H5N1-VN1203 infection may reduce the potential for transcriptional activation of chr. 6 genes, particularly within the MHC locus, and further implies that histone alterations may contribute to H5N1-VN1203-mediated down-regulation of antigen-presentation gene expression. For MERS-CoV, histone modification data offer a muddled picture, with enrichment and depletion found for both activating and repressive markers (Fig. S1) . Coupled with the ChIP-PCR of the promoter regions, these results suggest that histone modifications are not the driver of MERS-CoV-mediated antagonism of antigen presentation.