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

Vineet Menachery, Alexandra Schäfer, Kristin E. Burnum-Johnson, Hugh D. Mitchell, Amie J. Eisfeld, Kevin B. Walters, Carrie D. Nicora, Samuel O. Purvine, Cameron P. Casey, Matthew E. Monroe, Karl K. Weitz, Kelly G. Stratton, Bobbie Jo M. Webb-Robertson, Lisa E. Gralinski, Thomas O. Metz, Richard D. Smith, Katrina M. Waters, Amy C. Sims, Yoshihiro Kawaoka, Ralph S. Baric

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)E1012-E1021
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number5
DOIs
StatePublished - Jan 30 2018

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Coronavirus Infections
H5N1 Subtype Influenza A Virus
Antigen Presentation
Orthomyxoviridae
Epigenomics
Infection
Human Influenza
Down-Regulation
Histone Code
Viruses
Gene Expression
Severe Acute Respiratory Syndrome
Coronavirus
Vietnam
Influenza A virus
Gene Expression Regulation
Adaptive Immunity
DNA Methylation
Proteomics
Genes

Keywords

  • Antigen presentation
  • Coronavirus
  • DNA
  • Epigenetics
  • Influenza
  • Methylation

ASJC Scopus subject areas

  • General

Cite this

MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape. / Menachery, Vineet; 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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 5, 30.01.2018, p. E1012-E1021.

Research output: Contribution to journalArticle

Menachery, V, Schäfer, A, Burnum-Johnson, KE, Mitchell, HD, Eisfeld, AJ, Walters, KB, Nicora, CD, Purvine, SO, Casey, CP, Monroe, ME, Weitz, KK, Stratton, KG, Webb-Robertson, BJM, Gralinski, LE, Metz, TO, Smith, RD, Waters, KM, Sims, AC, Kawaoka, Y & Baric, RS 2018, 'MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape', Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 5, pp. E1012-E1021. https://doi.org/10.1073/pnas.1706928115
Menachery, Vineet ; 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. / MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 5. pp. E1012-E1021.
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AU - Mitchell, Hugh D.

AU - Eisfeld, Amie J.

AU - Walters, Kevin B.

AU - Nicora, Carrie D.

AU - Purvine, Samuel O.

AU - Casey, Cameron P.

AU - Monroe, Matthew E.

AU - Weitz, Karl K.

AU - Stratton, Kelly G.

AU - Webb-Robertson, Bobbie Jo M.

AU - Gralinski, Lisa E.

AU - Metz, Thomas O.

AU - Smith, Richard D.

AU - Waters, Katrina M.

AU - Sims, Amy C.

AU - Kawaoka, Yoshihiro

AU - Baric, Ralph S.

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N2 - 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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