Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists

Sarah A. Kopecky-Bromberg, Luis Martínez-Sobrido, Matthew Frieman, Ralph A. Baric, Peter Palese

Research output: Contribution to journalArticlepeer-review

491 Scopus citations

Abstract

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-β), and further examination revealed that these SARS-CoV proteins inhibit a key protein necessary for the expression of IFN-β, IRF-3. N protein dramatically inhibited expression from an NF-κB- 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.

Original languageEnglish
Pages (from-to)548-557
Number of pages10
JournalJournal of Virology
Volume81
Issue number2
DOIs
StatePublished - Jan 2007

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