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International Conference on SARS - one year after the (first) outbreak

08. - 11.05.2004, Lübeck

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Inhibition of interferon induction by the SARS-associated coronavirus

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  • Martin Spiegel - Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Freiburg, Germany
  • Andreas Pichlmair - Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Freiburg, Germany
  • Luis Martinez-Sobrido - Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA
  • Adolfo Garcia-Sastre - Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA
  • Otto Haller - Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Freiburg, Germany
  • corresponding author presenting/speaker Friedemann Weber - Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Freiburg, Germany

International Conference on SARS - one year after the (first) outbreak. Lübeck, 08.-11.05.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04sars12.08

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/sars2004/04sars063.shtml

Veröffentlicht: 26. Mai 2004

© 2004 Spiegel et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.

Gliederung

Text

We and others have previously shown that replication of SARS-CoV in cell culture can be efficiently inhibited by exogenously added interferon- (IFN-) beta ([1], [2]). Here, we investigated whether SARS-CoV is able to circumvent the induction of IFN to allow better growth in vivo. In cells infected with SARS-CoV, no endogenous IFN-beta transcripts were detected and no activation of the IFN-beta promoter occurred. To further analyze this block of IFN induction, we focused on IRF-3 which is the key transcription factor for the IFN-beta promoter. In uninfected cells, IRF-3 is present in the cytoplasm where it becomes activated by virus infection. Normally, IRF-3 then homodimerizes, translocates to the nucleus and transactivates the IFN-beta promoter. Nuclear translocation of IRF-3 was observed in SARS-CoV-infected cells. Homodimerization of IRF-3, however was not detectable. As a consequence, IRF-3 failed to bind to CBP, the essential coactivator of IFN transcription. Our data indicate that SARS-CoV circumvents IFN induction by inhibiting the homodimerization of IRF-3. Therefore, IRF-3 is unable to recruit the cofactor CBP, resulting in a block of IFN-beta transcription.

Gliederung

References

1.
Cinatl, J., B. Morgenstern, G. Bauer, P. Chandra, H. Rabenau, H.W. Doerr (2003). Lancet 362: 293-4
2.
Spiegel, M., A. Pichmair, O. Haller, F. Weber (2004): The antiviral effect of interferon-beta against SARS-Coronavirus is not mediated by MxA protein. J. Clin. Virol. in press