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

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

Author information

1
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555.
2
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
3
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354.
4
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706.
5
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706; yoshihiro.kawaoka@wisc.edu rbaric@email.unc.edu.
6
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 113-8654, Japan.
7
International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 113-8654, Japan.
8
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; yoshihiro.kawaoka@wisc.edu rbaric@email.unc.edu.
9
Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.

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:

DNA methylation; antigen presentation; coronavirus; epigenetics; influenza

PMID:
29339515
PMCID:
PMC5798318
DOI:
10.1073/pnas.1706928115
[Indexed for MEDLINE]
Free PMC Article

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