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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 in order 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 IFNγ dependent genes following infection with highly pathogenic viruses including influenza (H5N1-VN1203, H1N1-CA04) and coronaviruses (SARS-CoV, MERS-CoV). Categorizing by function, we observed down regulation of genes associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down regulation of antigen presentation genes and 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 genes; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Altogether, the results indicate a common approach utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.

Authors:
 [1];  [2]; ORCiD logo [3];  [3];  [4];  [5];  [3];  [3];  [3];  [3];  [3];  [3];  [3];  [2];  [3];  [3];  [3];  [2];  [6];  [2]
  1. Univ. of Texas Medical Branch, Galveston, TX (United States); Univ. of North Carolina, Chapel Hill, NC (United States)
  2. Univ. of North Carolina, Chapel Hill, NC (United States)
  3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  4. Univ. of Wisconsin, Madison, WI (United States)
  5. Univ. of Wisconsin, Madison, WI (United States); Southern Research, Frederick, MD (United States)
  6. Univ. of Wisconsin, Madison, WI (United States); Univ. of Tokyo, Tokyo (Japan)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1421337
Report Number(s):
PNNL-SA-126254
Journal ID: ISSN 0027-8424; 49636; WN9030198
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 115; Journal Issue: 5; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; MERS-CoV; antigen; epigenetic mechanisms; Environmental Molecular Sciences Laboratory; antigen presentation; epigenetics; coronavirus; influenza; DNA methylation

Citation Formats

Menachery, Vineet D., Schafer, 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, and Baric, Ralph S. MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape. United States: N. p., 2018. Web. doi:10.1073/pnas.1706928115.
Menachery, Vineet D., Schafer, 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. United States. doi:10.1073/pnas.1706928115.
Menachery, Vineet D., Schafer, 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, and Baric, Ralph S. Tue . "MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape". United States. doi:10.1073/pnas.1706928115. https://www.osti.gov/servlets/purl/1421337.
@article{osti_1421337,
title = {MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape},
author = {Menachery, Vineet D. and Schafer, Alexandra 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 Kawaoka, Yoshihiro and Baric, Ralph S.},
abstractNote = {Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways in order 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 IFNγ dependent genes following infection with highly pathogenic viruses including influenza (H5N1-VN1203, H1N1-CA04) and coronaviruses (SARS-CoV, MERS-CoV). Categorizing by function, we observed down regulation of genes associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down regulation of antigen presentation genes and 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 genes; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Altogether, the results indicate a common approach utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.},
doi = {10.1073/pnas.1706928115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 5,
volume = 115,
place = {United States},
year = {2018},
month = {1}
}

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Figures / Tables:

Table 1 Table 1: Down-regulated IFN-γ–responsive genes by classification

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    Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.