@article{70c46fffef1949a9b03166b7ccb2e6a3,
title = "MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape",
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.",
keywords = "Antigen presentation, Coronavirus, DNA, Epigenetics, Influenza, Methylation",
author = "Menachery, {Vineet D.} and Alexandra Sch{\"a}fer and Burnum-Johnson, {Kristin E.} and Mitchell, {Hugh D.} and Eisfeld, {Amie J.} and Walters, {Kevin B.} and Nicora, {Carrie D.} and Purvine, {Samuel O.} and Casey, {Cameron P.} and Monroe, {Matthew E.} and Weitz, {Karl K.} and Stratton, {Kelly G.} and Webb-Robertson, {Bobbie Jo M.} and Gralinski, {Lisa E.} and Metz, {Thomas O.} and Smith, {Richard D.} and Waters, {Katrina M.} and Sims, {Amy C.} and Yoshihiro Kawaoka and Baric, {Ralph S.}",
note = "Funding Information: Conflict of interest statement: Y.K. has received speaker{\textquoteright}s honoraria from Toyama Chemical and Astellas Inc.; and grant support from Chugai Pharmaceuticals, Daiichi Sankyo Pharmaceutical, Toyama Chemical, Tauns Laboratories, Inc., and Otsuka Pharmaceutical Co., Ltd. Y.K. is a founder of FluGen. Funding Information: ACKNOWLEDGMENTS. This research was supported by grants from NIH National Institute of Allergy and Infectious Diseases Grants U19AI100625 (to R.S.B.) and U19AI106772 (to Y.K.), and NIH National Institute of Aging Grant K99AG049092 (to V.D.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Proteo-mic analyses were performed in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy (DOE) Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory, and used capabilities developed under efforts supported by the National Institute of General Medical Sciences Proteomics Research Resource (GM103493). PNNL is operated by Battelle Memorial Institute for the DOE under Contract DE-AC05-76RLO1830. Funding Information: This research was supported by grants from NIH National Institute of Allergy and Infectious Diseases Grants U19AI100625 (to R.S.B.) and U19AI106772 (to Y.K.), and NIH National Institute of Aging Grant K99AG049092 (to V.D.M.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Proteo-mic analyses were performed in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy (DOE) Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory, and used capabilities developed under efforts supported by the National Institute of General Medical Sciences Proteomics Research Resource (GM103493). PNNL is operated by Battelle Memorial Institute for the DOE under Contract DE-AC05-76RLO1830.",
year = "2018",
month = jan,
day = "30",
doi = "10.1073/pnas.1706928115",
language = "English (US)",
volume = "115",
pages = "E1012--E1021",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "5",
}