Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design
Middle East respiratory syndrome coronavirus-encoded ORF8b strongly antagonizes IFN-β promoter activation: its implication for vaccine design
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DOI：
10.1007/s12275-019-9272-7
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发表时间：
2019-09-01
影响因子：
3
通讯作者：
Myoung, Jinjong
中科院分区：
文献类型：
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作者：
Lee, Jeong Yoon;Bae, Sojung;Myoung, Jinjong
中东呼吸综合征冠状病毒（MERS-CoV）是一种严重至致命性肺炎的病原体，特别是在有吸烟和慢性阻塞性肺疾病（COPD）等既存疾病的患者中。自2012年发现中东呼吸综合征冠状病毒以来，沙特阿拉伯半岛继续报告该病毒的传播。然而，除了2015年5月在韩国爆发的一次大规模疫情外，该地区很少流行。从韩国患者分离的流行MERS-CoV的基因组显示其与先前报道的菌株同源。MERS-CoV编码5种辅助蛋白，通常它们不参与基因组转录和复制，而是参与宿主先天免疫应答的病毒逃避。在这里，我们报告说，ORF 8b，MERS冠状病毒的辅助蛋白，强烈抑制MDA 5和RIG-I介导的激活干扰素β启动子活性，而下游信号分子在很大程度上不受影响。值得注意的是，ORF 8b以及ORF 4a和ORF 4 b的共表达显着下调了MDA 5蛋白水平。这些新的发现将有助于阐明病毒编码的逃避策略的机制，从而帮助设计针对致命MERS CoV感染的合理抗病毒对策。
Middle East respiratory syndrome coronavirus (MERS-CoV) is a causative agent of severe-to-fatal pneumonia especially in patients with pre-existing conditions, such as smoking and chronic obstructive pulmonary disease (COPD). MERS-CoV transmission continues to be reported in the Saudi Arabian Peninsula since its discovery in 2012. However, it has rarely been epidemic outside the area except one large outbreak in South Korea in May 2015. The genome of the epidemic MERS-CoV isolated from a Korean patient revealed its homology to previously reported strains. MERS-CoV encodes 5 accessory proteins and generally, they do not participate in the genome transcription and replication but rather are involved in viral evasion of the host innate immune responses. Here we report that ORF8b, an accessory protein of MERS-CoV, strongly inhibits both MDA5- and RIG-I-mediated activation of interferon beta promoter activity while downstream signaling molecules were left largely unaffected. Of note, MDA5 protein levels were significantly down-regulated by ORF8b and co-expression of ORF4a and ORF4b. These novel findings will facilitate elucidation of mechanisms of virus-encoded evasion strategies, thus helping design rationale antiviral countermeasures against deadly MERS-CoV infection.