Cryo-electron Microscopy Structure of the Swine Acute Diarrhea Syndrome Coronavirus Spike Glycoprotein Provides Insights into Evolution of Unique Coronavirus Spike Proteins
Cryo-electron Microscopy Structure of the Swine Acute Diarrhea Syndrome Coronavirus Spike Glycoprotein Provides Insights into Evolution of Unique Coronavirus Spike Proteins
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猪急性腹泻综合症冠状病毒刺突糖蛋白的冷冻电子显微镜结构为独特冠状病毒刺突蛋白的进化提供了见解
DOI：
10.1128/jvi.01301-20
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发表时间：
2020-11-01
影响因子：
5.4
通讯作者：
Ouyang, Songying
中科院分区：
文献类型：
--
作者：
Guan, Hongxin;Wang, Youwang;Ouyang, Songying
本文报道了猪急性腹泻综合征冠状病毒（SADS-CoV）刺突蛋白的原子分辨率融合前结构。SADS-CoV是一种致病性猪冠状病毒，导致猪致命疾病的大规模爆发，据报道能够在种间传播。我们描述了SADS-CoV刺突蛋白的整体结构，并对其主要结构元件进行了详细的分析。我们的研究结果和分析是一致的与以前的系统发育研究，并表明，SADS-CoV刺突蛋白是进化相关的β冠状病毒的刺突蛋白，具有很强的相似性，在S1-NTDs和S1-CTD的显着分歧。此外，我们还讨论了SADS-CoV刺突蛋白可能使用的免疫逃避策略。我们的研究提供了深入了解SADS-CoV刺突蛋白的结构和免疫逃避策略，并拓宽了对不同属冠状病毒刺突蛋白之间进化关系的理解。摘要冠状病毒（CoV）已经在人类和动物中引起了许多重大流行病，包括当前的2019冠状病毒病（COVID-19）大流行，这使得人们重新关注冠状病毒的进化和种间传播。猪急性腹泻综合征冠状病毒（SADS-CoV）是最近在中国南方的仔猪中发现的一种猪冠状病毒，与严重急性呼吸道综合征冠状病毒（SARS-CoV）来自同一属的马蹄蝠，据报道能够感染广泛物种的细胞，表明种间传播的潜力相当大。考虑到冠状病毒刺突（S）糖蛋白在宿主范围确定和病毒进入中的重要性，我们报告了融合前构象SADS-CoV S三聚体的冷冻电子显微镜（cryo-EM）结构，分辨率为3.55 μ m。我们的结构表明，SADS-CoV S三聚体假设intrasubunit四元包装模式，其中S1亚基N-末端结构域（S1-NTD）和S1亚基C-末端结构域（S1-CTD）的同一个原聚体包装在一起，面对对方躺下状态。SADS-CoV S具有几个独特的结构特征，可以促进免疫逃逸，例如S三聚体的相对紧凑的结构和通过聚糖屏蔽的表位掩蔽。SADS-CoV S与其他冠状病毒属的刺突蛋白的比较表明，SADS-CoV S的结构特征与其他属的刺突蛋白的结构特征在进化上相关，而不是典型的SADS-CoV S的刺突蛋白。这些数据为SADS-CoV和其他冠状病毒的刺突糖蛋白之间的进化关系提供了新的见解，并扩展了我们对其结构和功能多样性的理解。在这篇文章中，我们报告了猪急性腹泻综合征冠状病毒（SADS-CoV）刺突蛋白的原子分辨率融合前结构。SADS-CoV是一种致病性猪冠状病毒，导致猪致命疾病的大规模爆发，据报道能够在种间传播。我们描述了SADS-CoV刺突蛋白的整体结构，并对其主要结构元件进行了详细的分析。我们的研究结果和分析是一致的与以前的系统发育研究，并表明，SADS-CoV刺突蛋白是进化相关的β冠状病毒的刺突蛋白，具有很强的相似性，在S1-NTDs和S1-CTD的显着分歧。此外，我们还讨论了SADS-CoV刺突蛋白可能使用的免疫逃避策略。我们的研究提供了深入了解SADS-CoV刺突蛋白的结构和免疫逃避策略，并拓宽了对不同属冠状病毒刺突蛋白之间进化关系的理解。
In this article, we report the atomic-resolution prefusion structure of the spike protein from swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV is a pathogenic alphacoronavirus that was responsible for a large-scale outbreak of fatal disease in pigs and that was reported to be capable of interspecies transmission. We describe the overall structure of the SADS-CoV spike protein and conducted a detailed analysis of its main structural elements. Our results and analyses are consistent with those of previous phylogenetic studies and suggest that the SADS-CoV spike protein is evolutionarily related to the spike proteins of betacoronaviruses, with a strong similarity in S1-NTDs and a marked divergence in S1-CTDs. Moreover, we discuss the possible immune evasion strategies used by the SADS-CoV spike protein. Our study provides insights into the structure and immune evasion strategies of the SADS-CoV spike protein and broadens the understanding of the evolutionary relationships between coronavirus spike proteins of different genera. ABSTRACT Coronaviruses (CoV) have caused a number of major epidemics in humans and animals, including the current pandemic of coronavirus disease 2019 (COVID-19), which has brought a renewed focus on the evolution and interspecies transmission of coronaviruses. Swine acute diarrhea syndrome coronavirus (SADS-CoV), which was recently identified in piglets in southern China, is an alphacoronavirus that originates from the same genus of horseshoe bats as severe acute respiratory syndrome CoV (SARS-CoV) and that was reported to be capable of infecting cells from a broad range of species, suggesting a considerable potential for interspecies transmission. Given the importance of the coronavirus spike (S) glycoprotein in host range determination and viral entry, we report a cryo-electron microscopy (cryo-EM) structure of the SADS-CoV S trimer in the prefusion conformation at a 3.55-Å resolution. Our structure reveals that the SADS-CoV S trimer assumes an intrasubunit quaternary packing mode in which the S1 subunit N-terminal domain (S1-NTD) and the S1 subunit C-terminal domain (S1-CTD) of the same protomer pack together by facing each other in the lying-down state. SADS-CoV S has several distinctive structural features that may facilitate immune escape, such as a relatively compact architecture of the S trimer and epitope masking by glycan shielding. Comparison of SADS-CoV S with the spike proteins of the other coronavirus genera suggested that the structural features of SADS-CoV S are evolutionarily related to those of the spike proteins of the other genera rather than to the spike protein of a typical alphacoronavirus. These data provide new insights into the evolutionary relationship between spike glycoproteins of SADS-CoV and those of other coronaviruses and extend our understanding of their structural and functional diversity. IMPORTANCE In this article, we report the atomic-resolution prefusion structure of the spike protein from swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV is a pathogenic alphacoronavirus that was responsible for a large-scale outbreak of fatal disease in pigs and that was reported to be capable of interspecies transmission. We describe the overall structure of the SADS-CoV spike protein and conducted a detailed analysis of its main structural elements. Our results and analyses are consistent with those of previous phylogenetic studies and suggest that the SADS-CoV spike protein is evolutionarily related to the spike proteins of betacoronaviruses, with a strong similarity in S1-NTDs and a marked divergence in S1-CTDs. Moreover, we discuss the possible immune evasion strategies used by the SADS-CoV spike protein. Our study provides insights into the structure and immune evasion strategies of the SADS-CoV spike protein and broadens the understanding of the evolutionary relationships between coronavirus spike proteins of different genera.