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Originally published as JGV in Press, 10.1099/vir.0.013599-0 on July 22, 2009 J Gen Virol 90 (2009), 2686-2694; DOI 10.1099/vir.0.013599-0

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Interferon priming enables cells to partially overturn the SARS coronavirus-induced block in innate immune activation

Thomas Kuri1, Xiaonan Zhang2, Matthias Habjan1, Luis Martínez-Sobrido3, Adolfo García-Sastre4, Zhenghong Yuan2 and Friedemann Weber1

1 Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany
2 Research Unit, Shanghai Public Health Clinical Center, and Key Laboratory of Medical Molecular Virology, Fudan University, Shanghai, PR China
3 School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA
4 Department of Microbiology, Department of Medicine (Division of Infectious Diseases) and Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, NY 10029, USA

Correspondence
Friedemann Weber
friedemann.weber{at}uniklinik-freiburg.de

SARS coronavirus (SARS-CoV) is known to efficiently suppress the induction of antiviral type I interferons (IFN-{alpha}/β) in non-lymphatic cells through inhibition of the transcription factor IRF-3. Plasmacytoid dendritic cells, in contrast, respond to infection with production of high levels of IFNs. Here, we show that pretreatment of non-lymphatic cells with small amounts of IFN-{alpha} (IFN priming) partially overturns the block in IFN induction imposed by SARS-CoV. IFN priming combined with SARS-CoV infection substantially induced genes for IFN induction, IFN signalling, antiviral effector proteins, ubiquitination and ISGylation, antigen presentation and other cytokines and chemokines, whereas each individual treatment had no major effect. Curiously, however, despite this typical IFN response, neither IRF-3 nor IRF-7 was transported to the nucleus as a sign of activation. Taken together, our results suggest that (i) IFN, as it is produced by plasmacytoid dendritic cells, could enable tissue cells to launch a host response to SARS-CoV, (ii) IRF-3 and IRF-7 may be active at subdetectable levels, and (iii) SARS-CoV does not activate IRF-7.

Two supplementary tables showing oligonucleotide primers used for RT-PCR analyses and global gene expression in IFN-primed and SARS-CoV-infected 293lp cells are available with the online version of this paper.







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