SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
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DOI：
10.1080/22221751.2020.1780953
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发表时间：
2020-01-01
影响因子：
13.2
通讯作者：
Kok, Kin-Hang
中科院分区：
文献类型：
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作者：
Yuen, Chun-Kit;Lam, Joy-Yan;Kok, Kin-Hang
由新型 SARS-CoV-2 病毒引起的 2019 冠状病毒病 (COVID-19) 目前正在引起巨大的全球健康问题。自2019年12月首次爆发以来，疫情已在全球造成超过580万人感染（截至2020年5月29日），逾35万人死亡。早期病毒介导的免疫抑制被认为是 SARS-CoV-2 感染的独特特征之一，并且至少部分促成了病毒发病机制。在这项研究中，我们鉴定了 SARS-CoV-2 的关键病毒干扰素拮抗剂，并将其与两种充分表征的 SARS-CoV 干扰素拮抗剂 PLpro 和 orf6 进行比较。在这里，我们证明了 SARS-CoV-2 nsp13、nsp14、nsp15 和 orf6，但不是独特的 orf8，可以有效抑制初级干扰素产生和干扰素信号传导。尽管 SARS-CoV PLpro 因其有效的干扰素拮抗、去泛素酶和蛋白酶活性而闻名，但 SARS-CoV-2 PLpro 尽管与 SARS-CoV 具有高度的氨基酸序列相似性，但失去了干扰素拮抗和去泛素酶活性。在 27 种病毒蛋白中，SARS-CoV-2 orf6 对初级干扰素产生和干扰素信号传导的抑制最强。 Orf6 缺失的 SARS-CoV-2 可考虑用于开发针对 COVID-19 的鼻内活减毒疫苗。
The Coronavirus disease 2019 (COVID-19), which is caused by the novel SARS-CoV-2 virus, is now causing a tremendous global health concern. Since its first appearance in December 2019, the outbreak has already caused over 5.8 million infections worldwide (till 29 May 2020), with more than 0.35 million deaths. Early virus-mediated immune suppression is believed to be one of the unique characteristics of SARS-CoV-2 infection and contributes at least partially to the viral pathogenesis. In this study, we identified the key viral interferon antagonists of SARS-CoV-2 and compared them with two well-characterized SARS-CoV interferon antagonists, PLpro and orf6. Here we demonstrated that the SARS-CoV-2 nsp13, nsp14, nsp15 and orf6, but not the unique orf8, could potently suppress primary interferon production and interferon signalling. Although SARS-CoV PLpro has been well-characterized for its potent interferon-antagonizing, deubiquitinase and protease activities, SARS-CoV-2 PLpro, despite sharing high amino acid sequence similarity with SARS-CoV, loses both interferon-antagonising and deubiquitinase activities. Among the 27 viral proteins, SARS-CoV-2 orf6 demonstrated the strongest suppression on both primary interferon production and interferon signalling. Orf6-deleted SARS-CoV-2 may be considered for the development of intranasal live-but-attenuated vaccine against COVID-19.