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.

Targeting of host antigen presentation has significant implications for pathogenesis of both MERS-CoV and H5N1-VN1203. Unlike SARS-CoV infection, which is limited to pneumocytes and ciliated airway epithelium in the lung (19) , MERS-CoV has broader tropism, infecting not only nonciliated airway epithelial cells and type 1/2 pneumocytes in the lung, but a number of immune cell populations, including T cells, macrophages, and dendritic cells in vitro (20) (21) (22) ; similarly, a number of H5N1-VN1203 strains have been reported to infect both macrophages and dendritic cells in vitro (23, 24) . In the context of antigen presentation, the expanded tropism of both viruses potentially impacts systemic aspects of adaptive immunity and memory responses. For H5N1 strains, modulation of antigen presentation may contribute to the inefficacy of the CD8 T-cell response during acute infection (25) and marginal, waning memory responses overall (26) . Similarly, MERS-CoV infection has been characterized by uneven and often marginal antibody serum neutralization in recovering patients (27, 28) . For both viruses, manipulation of antigen presentation may contribute to these diminished responses and may have important ramifications for both vaccine designs.