Inhibition of Beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3.

Abstract

Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus termed SARS-CoV. We and others have previously shown that the replication of SARS-CoV can be suppressed by exogenously added interferon (IFN), a cytokine which is normally synthesized by cells as a reaction to virus infection. Here, we demonstrate that SARS-CoV escapes IFN-mediated growth inhibition by preventing the induction of IFN-beta. In SARS-CoV-infected cells, no endogenous IFN-beta transcripts and no IFN-beta promoter activity were detected. Nevertheless, the transcription factor interferon regulatory factor 3 (IRF-3), which is essential for IFN-beta promoter activity, was transported from the cytoplasm to the nucleus early after infection with SARS-CoV. However, at a later time point in infection, IRF-3 was again localized in the cytoplasm. By contrast, IRF-3 remained in the nucleus of cells infected with the IFN-inducing control virus Bunyamwera delNSs. Other signs of IRF-3 activation such as hyperphosphorylation, homodimer formation, and recruitment of the coactivator CREB-binding protein (CBP) were found late after infection with the control virus but not with SARS-CoV. Our data suggest that nuclear transport of IRF-3 is an immediate-early reaction to virus infection and may precede its hyperphosphorylation, homodimer formation, and binding to CBP. In order to escape activation of the IFN system, SARS-CoV appears to block a step after the early nuclear transport of IRF-3.

• Authors: Martin Spiegel, Andreas Pichlmair, Luis Martínez-Sobrido, Jerome Cros, Adolfo García-Sastre, Otto Haller, Friedemann Weber
• Journal: Journal of virology (J Virol) Vol. 79 Issue 4 Pg. 2079-86 (Feb 2005) ISSN: 0022-538X [Print] United States
• PMID: 15681410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Interferon Regulatory Factor-3
• Transcription Factors
• Interferon-beta

Topics

• Animals
• Chlorocebus aethiops
• DNA-Binding Proteins (metabolism)
• Interferon Regulatory Factor-3
• Interferon-beta (metabolism)
• Phosphorylation
• Severe acute respiratory syndrome-related coronavirus (physiology)
• Transcription Factors (metabolism)
• Vero Cells