Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists
Severe acute respiratory syndrome coronavirus open reading frame (ORF) 3b, ORF 6, and nucleocapsid proteins function as interferon antagonists
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DOI：
10.1128/jvi.01782-06
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发表时间：
2007-01-01
影响因子：
5.4
通讯作者：
Palese, Peter
中科院分区：
文献类型：
--
作者：
Kopecky-Bromberg, Sarah A.;Martinez-Sobrido, Luis;Palese, Peter
严重急性呼吸综合征冠状病毒（SARS - CoV）对人类具有高度致病性，死亡率接近10%。这种高致病性表明SARS - CoV已形成克服宿主固有免疫反应的机制。现已确定SARS - CoV的开放阅读框（ORF）3b、ORF6和N蛋白可拮抗干扰素，而干扰素是固有免疫反应的关键成分。这三种蛋白均抑制β干扰素（IFN - β）的表达，进一步研究表明，这些SARS - CoV蛋白抑制IFN - β表达所必需的一种关键蛋白——IRF - 3。N蛋白显著抑制NF - κB响应启动子的表达。在感染仙台病毒后，这三种蛋白都能抑制干扰素刺激反应元件（ISRE）启动子的表达，而在干扰素处理后，只有ORF 3b和ORF 6蛋白能够抑制ISRE启动子的表达。这表明N蛋白仅抑制干扰素的合成，而ORF 3b和ORF 6蛋白既抑制干扰素合成又抑制其信号传导。ORF 6蛋白（而非ORF 3b或N蛋白）抑制STAT1的核转位，但不抑制其磷酸化。因此，似乎SARS - CoV的这三种干扰素拮抗剂通过不同机制抑制干扰素反应。
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-beta), and further examination revealed that these SARS-CoV proteins inhibit a key protein necessary for the expression of IFN-beta, 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.