The ORF8 Protein of SARS-CoV-2 Modulates the Spike Protein and Its Implications in Viral Transmission.
The ORF8 Protein of SARS-CoV-2 Modulates the Spike Protein and Its Implications in Viral Transmission.
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DOI：
10.3389/fmicb.2022.883597
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发表时间：
2022
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
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作者：
目前，新冠肺炎 (COVID-19) 是由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起的全球大流行。随着容易出错的基于 RNA 的基因组的快速传播，已经从基因上鉴定出了几种主要的 SARS-CoV-2 变体。刺突蛋白的突变对于受体结合和融合至关重要，已对其对病毒传播的贡献进行了深入研究。尽管如此，其他病毒蛋白及其突变在 SARS-CoV-2 生命周期和传播中的重要性仍然广为人知。在这里，我们报告了辅助蛋白 ORF8 在调节刺突蛋白的水平和加工方面的强大效力。 ORF8蛋白的表达不影响增殖，但影响刺突蛋白的表达，这可能导致假病毒粒子表面刺突蛋白较少，因此感染潜力较小。在蛋白质水平上，ORF8表达以剂量依赖性方式导致刺突蛋白的下调和S1/S2切割不足。 ORF8 主要在 S1 结构域与刺突蛋白表现出强烈的相互作用，并通过多种途径介导其降解。蛋白质稳定性降低的主要临床分离 ORF8 变体表现出病毒传播能力增强，且不影响其对 HLA-A2 的抑制作用。尽管通过使用高度传播的临床刺突变体观察到刺突蛋白水平和刺突假病毒产量的增加，但 ORF8 介导的下调没有显着影响。由于 ORF8 对于免疫监视很重要，并且可能是体内病毒适应性所必需的，因此刺突蛋白的改变可能是 SARS-CoV-2 使用的一种可选策略，通过逃避 ORF8 的抑制作用来促进病毒传播。因此，我们的报告强调了 ORF8 在 SARS-CoV-2 刺突蛋白产生、成熟和可能的进化中的重要性。
COVID-19 is currently global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Accompanying the rapid spread of the error-prone RNA-based genome, several dominant SARS-CoV-2 variants have been genetically identified. The mutations in the spike protein, which are essential for receptor binding and fusion, have been intensively investigated for their contributions to viral transmission. Nevertheless, the importance of other viral proteins and their mutations in SARS-CoV-2 lifecycle and transmission remains fairly understood. Here, we report the strong potency of an accessory protein ORF8 in modulating the level and processing of the spike protein. The expression of ORF8 protein does not affect propagation but expression of spike protein, which may lead to pseudovirions with less spike protein on the surface, therefore less infection potential. At the protein level, ORF8 expression led to downregulation and insufficient S1/S2 cleavage of the spike protein in a dose-dependent manner. ORF8 exhibits a strong interaction with the spike protein mainly at S1 domains and mediates its degradation through multiple pathways. The dominant clinical isolated ORF8 variants with the reduced protein stability exhibited the increased capacity of viral transmission without compromising their inhibitory effects on HLA-A2. Although the increase in spike protein level and Spike pseudovirus production observed by using highly transmissible clinical spike variants, there was no significant compromise in ORF8-mediated downregulation. Because ORF8 is important for immune surveillance and might be required for viral fitness in vivo, the alteration of the spike protein might be an optional strategy used by SARS-CoV-2 to promote viral transmission by escaping the inhibitory effects of ORF8. Therefore, our report emphasized the importance of ORF8 in SARS-CoV-2 spike protein production, maturation, and possible evolution.
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影响因子：
64.5
作者：
Li Q;Nie J;Wu J;Zhang L;Ding R;Wang H;Zhang Y;Li T;Liu S;Zhang M;Zhao C;Liu H;Nie L;Qin H;Wang M;Lu Q;Li X;Liu J;Liang H;Shi Y;Shen Y;Xie L;Zhang L;Qu X;Xu W;Huang W;Wang Y
通讯作者：
Wang Y
DOI：
10.1126/science.abe8499
发表时间：
2020-12-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hou YJ;Chiba S;Halfmann P;Ehre C;Kuroda M;Dinnon KH 3rd;Leist SR;Schäfer A;Nakajima N;Takahashi K;Lee RE;Mascenik TM;Graham R;Edwards CE;Tse LV;Okuda K;Markmann AJ;Bartelt L;de Silva A;Margolis DM;Boucher RC;Randell SH;Suzuki T;Gralinski LE;Kawaoka Y;Baric RS
通讯作者：
Baric RS
DOI：
10.1177/11769343211003079
发表时间：
2021
期刊：
Evolutionary bioinformatics online
影响因子：
--
作者：
Fahmi M;Kitagawa H;Yasui G;Kubota Y;Ito M
通讯作者：
Ito M
影响因子：
64.5
作者：
Liu C;Ginn HM;Dejnirattisai W;Supasa P;Wang B;Tuekprakhon A;Nutalai R;Zhou D;Mentzer AJ;Zhao Y;Duyvesteyn HME;López-Camacho C;Slon-Campos J;Walter TS;Skelly D;Johnson SA;Ritter TG;Mason C;Costa Clemens SA;Gomes Naveca F;Nascimento V;Nascimento F;Fernandes da Costa C;Resende PC;Pauvolid-Correa A;Siqueira MM;Dold C;Temperton N;Dong T;Pollard AJ;Knight JC;Crook D;Lambe T;Clutterbuck E;Bibi S;Flaxman A;Bittaye M;Belij-Rammerstorfer S;Gilbert SC;Malik T;Carroll MW;Klenerman P;Barnes E;Dunachie SJ;Baillie V;Serafin N;Ditse Z;Da Silva K;Paterson NG;Williams MA;Hall DR;Madhi S;Nunes MC;Goulder P;Fry EE;Mongkolsapaya J;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
1.3
作者：
Alkhansa A;Lakkis G;El Zein L
通讯作者：
El Zein L