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

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
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  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)
+ Show Author Affiliations

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.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC05-76RL01830
OSTI ID:
1421337
Report Number(s):
PNNL-SA--126254; 49636; WN9030198
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 5 Vol. 115; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English

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  • The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/mdjq-3337
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Cited By (11)

PNNL DataHub Project Omics-LHV Profiling of Host Response to Influenza Infection Post-Processed Data Package DOIs dataset January 2021
Icl104 dataset January 2020
Icl105 dataset January 2020
Icl106 dataset January 2020
Inhp001 dataset January 2020
Mcl004 dataset January 2020
Mcl005 dataset January 2020
PNNL DataHub NIAID Program Project: Modeling Host Responses to Understand Severe Human Virus Infections, Multi-Omic Viral Dataset Catalog Collection dataset January 2023
Recent Aspects on the Pathogenesis Mechanism, Animal Models and Novel Therapeutic Interventions for Middle East Respiratory Syndrome Coronavirus Infections journal March 2019
Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection text January 2020
Omics Lethal Human Viruses Project Profiling of the Host Response to MERS-CoV Infection, Processed Experimental Dataset Catalog dataset January 2021

Figures / Tables (7)

Table 1(p. 2)table Table 1
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59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
DNA methylation
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MERS-CoV
antigen
antigen presentation
coronavirus
epigenetic mechanisms
epigenetics
influenza