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

Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E1012-E1021. doi: 10.1073/pnas.1706928115. Epub 2018 Jan 16.


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.

Keywords: DNA methylation; antigen presentation; coronavirus; epigenetics; influenza.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigenic Variation
  • Cell Line
  • Chlorocebus aethiops
  • DNA Methylation
  • Dogs
  • Down-Regulation
  • Epigenesis, Genetic*
  • Histones / chemistry
  • Humans
  • Influenza A Virus, H5N1 Subtype / pathogenicity*
  • Madin Darby Canine Kidney Cells
  • Major Histocompatibility Complex
  • Middle East Respiratory Syndrome Coronavirus / pathogenicity*
  • Mutation
  • Open Reading Frames
  • Proteomics
  • Vero Cells


  • Histones