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.

In contrast, a MERS-CoV mutant strain lacking all four accessory ORF proteins produced robust down-regulation of both HLA-A and -C, despite a 100-fold replication attenuation relative to WT control virus. These results suggest that MERS-CoV entry or initial steps of infection trigger antagonism of antigen presentation. One possibility is stimulation of host processes that directly or indirectly result in reduction of the antigen-presentation molecules. For example, MERS-CoV infection may stimulate depression of host gene regulation, resulting in increased competition for transcription factors driving MHC expression. Alternatively, activation of DNA methylation pathways may be initiated by MERS-CoV infection, resulting in regulation of host constitutive processes as well as dipeptidyl peptidase 4 receptor expression (18) . Together, the mutant virus data from both viruses suggest that complex host-pathogen interaction dictate epigenetic-based antagonism of antigen presentation.