Early Gene Expression Events in Ferrets in Response to SARS Coronavirus Infection Versus Direct interferon-alpha2b Stimulation

Virology. 2011 Jan 5;409(1):102-12. doi: 10.1016/j.virol.2010.10.002. Epub 2010 Oct 28.

Abstract

Type I interferons (IFNs) are essential to the clearance of viral diseases, however, a clear distinction between genes upregulated by direct virus-cell interactions and genes upregulated by secondary IFN production has not been made. Here, we investigated differential gene regulation in ferrets upon subcutaneous administration of IFN-α2b and during SARS-CoV infection. In vivo experiments revealed that IFN-α2b causes STAT1 phosphorylation and upregulation of abundant IFN response genes (IRGs), chemokine receptors, and other genes that participate in phagocytosis and leukocyte transendothelial migration. During infection with SARS-CoV not only a variety of IRGs were upregulated, but also a significantly broader range of genes involved in cell migration and inflammation. This work allowed dissection of several molecular signatures present during SARS-CoV which are part of a robust IFN antiviral response. These signatures can be useful markers to evaluate the status of IFN responses during a viral infection and specific features of different viruses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Ferrets / virology*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / immunology*
  • Male
  • Molecular Sequence Data
  • Proteins / genetics
  • Proteins / metabolism*
  • Recombinant Proteins
  • SARS Virus / pathogenicity*
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Sequence Analysis, DNA
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / virology
  • Up-Regulation

Substances

  • Interferon alpha-2
  • Interferon-alpha
  • Proteins
  • Recombinant Proteins
  • STAT1 Transcription Factor

Associated data

  • GENBANK/EU835483
  • GENBANK/EU835484
  • GENBANK/EU835487
  • GENBANK/EU835488
  • GENBANK/EU835489
  • GENBANK/EU835493
  • GENBANK/EU835985
  • GENBANK/EU835986
  • GENBANK/EU835987
  • GENBANK/EU835988
  • GENBANK/EU835989
  • GENBANK/EU835990
  • GEO/GSE22581