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Title: Pathogenic Influenza Viruses and Coronaviruses Utilize Similar and Contrasting Approaches To Control Interferon-Stimulated Gene Responses

Journal Article · · mBio (Online)
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  1. Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Epidemiology
  2. Univ. of Wisconsin, Madison, WI (United States). School of Veterinary Medicine. Dept. of Pathobiological Sciences. Influenza Research Inst.
  3. Univ. of Washington, Seattle, WA (United States). School of Medicine. Dept. of Microbiology
  4. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Biological Sciences Division
  5. Univ. of Washington, Seattle, WA (United States). School of Medicine. Dept. of Microbiology; Univ. of Washington, Seattle, WA (United States). Washington National Primate Research Center
  6. Univ. of Wisconsin, Madison, WI (United States). School of Veterinary Medicine. Dept. of Pathobiological Sciences. Influenza Research Inst.; Univ. of Tokyo (Japan). Inst. of Medicine. Dept. of Microbiology and Immunology. Division of Virology; Univ. of Tokyo (Japan). Dept. of Special Pathogens. Inst. of Medical Science. International Research Center for Infectious Diseases; ERATO Infection-Induced Host Responses Project, Saitama (Japan)
  7. Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Epidemiology; Univ. of North Carolina, Chapel Hill, NC (United States). Dept. of Microbiology and Immunology
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The broad range and diversity of interferon-stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis of the global ISG response and subsequent viral antagonism has yet to be examined. Employing models of the human airway, transcriptomics and proteomics datasets were used to compare ISG response patterns following highly pathogenic H5N1 avian influenza (HPAI) A virus, 2009 pandemic H1N1, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV) infection. The results illustrated distinct approaches utilized by each virus to antagonize the global ISG response. In addition, the data revealed that highly virulent HPAI virus and MERS-CoV induce repressive histone modifications, which downregulate expression of ISG subsets. Notably, influenza A virus NS1 appears to play a central role in this histone-mediated downregulation in highly pathogenic influenza strains. Together, the work demonstrates the existence of unique and common viral strategies for controlling the global ISG response and provides a novel avenue for viral antagonism via altered histone modifications.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC06-76RL01830
OSTI ID:
1626128
Journal Information:
mBio (Online), Vol. 5, Issue 3; ISSN 2150-7511
Publisher:
American Society for Microbiology (ASM)Copyright Statement
Country of Publication:
United States
Language:
English

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Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS‐CoV, MERS‐CoV, and 2019‐nCoV journal February 2020
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DeltaNeTS+: elucidating the mechanism of drugs and diseases using gene expression and transcriptional regulatory networks journal March 2021
Mouse-adapted MERS coronavirus causes lethal lung disease in human DPP4 knockin mice journal March 2017
MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape
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Sm018 dataset January 2020
Sm031 dataset January 2020
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Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways journal July 2015
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Sm023 dataset January 2020
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Sm035 dataset January 2020
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