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Group 2 coronaviruses prevent immediate early interferon induction by protection of viral RNA from host cell

Gijs A Versteeg1, Peter J Bredenbeek, Sjoerd H E van den Worm

  • 1Molecular Virology Laboratory, Department of Medical Microbiology, Center of Infectious Diseases, Leiden University Medical Center, LUMC E4-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

Virology
|February 24, 2007
PubMed

Insights

Coronaviruses like MHV and SARS-CoV prevent interferon induction by shielding viral RNA from host sensors, not by inactivating key transcription factors like IRF3.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Viruses often encode antagonists to inhibit the host interferon (IFN) response.
  • Interferon-regulatory factor 3 (IRF3) is crucial for inducing IFN transcription.
  • Coronaviruses (CoVs) are known to interfere with host antiviral mechanisms.

Purpose of the Study:

  • To investigate the mechanism by which murine hepatitis coronavirus (MHV) and SARS-coronavirus (SARS-CoV) prevent interferon induction.
  • To determine if CoVs inactivate IRF3-mediated transcription regulation or interfere with viral RNA detection.

Main Methods:

  • Infection of fibroblasts with MHV and SARS-CoV.
  • Assessing nuclear translocation of IRF3.
  • Measuring IFN mRNA transcription.
  • Evaluating IFN induction by exogenous stimuli (poly (I:C) and Sendai virus).

Main Results:

  • MHV and SARS-CoV infection did not lead to IRF3 nuclear translocation or IFN mRNA induction.
  • These CoVs did not inhibit IFN induction triggered by poly (I:C) or Sendai virus.
  • The results suggest CoVs prevent the detection of viral RNA by cellular sensors.

Conclusions:

  • Coronaviruses appear to prevent interferon induction primarily by shielding their RNA from host cell sensors.
  • This mechanism, rather than direct inactivation of IRF3, is likely the main strategy CoVs use to evade the innate immune response.

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