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Journal of Virology, January 2007, p. 548-557, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01782-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists{triangledown}

Sarah A. Kopecky-Bromberg,1 Luis Martínez-Sobrido,1 Matthew Frieman,2 Ralph A. Baric,2 and Peter Palese1*

Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029-6574,1 University of North Carolina, 2107 McGaveran-Greenberg Hall CB 7435, Chapel Hill, North Carolina 275992

Received 16 August 2006/ Accepted 27 October 2006

The severe acute respiratory syndrome coronavirus (SARS-CoV) is highly pathogenic in humans, with a death rate near 10%. This high pathogenicity suggests that SARS-CoV has developed mechanisms to overcome the host innate immune response. It has now been determined that SARS-CoV open reading frame (ORF) 3b, ORF 6, and N proteins antagonize interferon, a key component of the innate immune response. All three proteins inhibit the expression of beta interferon (IFN-ß), and further examination revealed that these SARS-CoV proteins inhibit a key protein necessary for the expression of IFN-ß, IRF-3. N protein dramatically inhibited expression from an NF-{kappa}B-responsive promoter. All three proteins were able to inhibit expression from an interferon-stimulated response element (ISRE) promoter after infection with Sendai virus, while only ORF 3b and ORF 6 proteins were able to inhibit expression from the ISRE promoter after treatment with interferon. This indicates that N protein inhibits only the synthesis of interferon, while ORF 3b and ORF 6 proteins inhibit both interferon synthesis and signaling. ORF 6 protein, but not ORF 3b or N protein, inhibited nuclear translocation but not phosphorylation of STAT1. Thus, it appears that these three interferon antagonists of SARS-CoV inhibit the interferon response by different mechanisms.

* Corresponding author. Mailing address: Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029-6574. Phone: (212) 241-7318. Fax: (212) 534-1684. E-mail: peter.palese{at}mssm.edu.

{triangledown} Published ahead of print on 15 November 2006.

Journal of Virology, January 2007, p. 548-557, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01782-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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