Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses

Vineet D. Menachery, Amie J. Eisfeld, Alexandra Schäfer, Laurence Josset, Amy C. Sims, Sean Proll, Shufang Fan, Chengjun Li, Gabriele Neumann, Susan C. Tilton, Jean Chang, Lisa E. Gralinski, Casey Long, Richard Green, Christopher M. Williams, Jeffrey Weiss, Melissa M. Matzke, Bobbie Jo Webb-Robertson, Athena A. Schepmoes, Anil K. ShuklaThomas O. Metz, Richard D. Smith, Katrina M. Waters, Michael G. Katze, Yoshihiro Kawaoka, Ralph S. Baric

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

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 histonemediated 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.

Original languageEnglish (US)
Article numbere01174-14
JournalmBio
Volume5
Issue number3
DOIs
StatePublished - May 20 2014
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Virology

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    Menachery, V. D., Eisfeld, A. J., Schäfer, A., Josset, L., Sims, A. C., Proll, S., Fan, S., Li, C., Neumann, G., Tilton, S. C., Chang, J., Gralinski, L. E., Long, C., Green, R., Williams, C. M., Weiss, J., Matzke, M. M., Webb-Robertson, B. J., Schepmoes, A. A., ... Baric, R. S. (2014). Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses. mBio, 5(3), [e01174-14]. https://doi.org/10.1128/mBio.01174-14