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

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  • Menachery, Vineet D.
    • Other Affiliation: University of Texas Medical Branch
  • Schäfer, Alexandra
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Burnum-Johnson, Kristin E.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Mitchell, Hugh D.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Eisfeld, Amie J.
    • Other Affiliation: University of Wisconsin-Madison
  • Walters, Kevin B.
    • Other Affiliation: University of Wisconsin-Madison
  • Nicora, Carrie D.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Purvine, Samuel O.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Casey, Cameron P.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Monroe, Matthew E.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Weitz, Karl K.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Stratton, Kelly G.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Webb-Robertson, Bobbie-Jo M.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Gralinski, Lisa E.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Metz, Thomas O.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Smith, Richard D.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Waters, Katrina M.
    • Other Affiliation: Pacific Northwest National Laboratory
  • Sims, Amy C.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Kawaoka, Yoshihiro
    • Other Affiliation: University of Tokyo
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems-based approach, we examined differential regulation of IFN-γ–dependent genes following infection with robust respiratory viruses including influenza viruses [A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009 (H1N1-CA04)] and coronaviruses [severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV)]. Categorizing by function, we observed down-regulation of gene expression associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down-regulation of antigen-presentation gene expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation, rather than histone modification, plays a crucial role in MERS-CoV–mediated antagonism of antigen-presentation gene expression; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common mechanism utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Proceedings of the National Academy of Sciences of the United States of America
Journal volume
  • 115
Journal issue
  • 5
Page start
  • E1012
Page end
  • E1021
Language
  • English
ISSN
  • 0027-8424

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