The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint.
The Glycan-Binding Trait of the Sarbecovirus Spike N-Terminal Domain Reveals an Evolutionary Footprint.
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DOI：
10.1128/jvi.00958-22
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发表时间：
2022-08-10
影响因子：
5.4
通讯作者：
Shi, Zheng-Li
中科院分区：
文献类型：
--
作者：
Guo, Hua;Li, Ang;Lin, Hao-Feng;Liu, Mei-Qin;Chen, Jing;Jiang, Ting-Ting;Li, Bei;Wang, Yi;Letko, Michael C.;Peng, Wenjie;Shi, Zheng-Li
Sarbecovirus病毒粒子上的刺突蛋白含有两个外部突出结构域：功能不清楚的N-末端结构域（NTD）和结合宿主受体的C-末端结构域（CTD），允许病毒进入和感染。虽然CTD在治疗干预方面得到了很好的研究，但NTD在许多冠状病毒中的作用还远未得到很好的理解。在这里，我们证明，穗NTD从SARS-CoV-2和其他Sarbecoviruses结合到身份不明的聚糖在体外类似于其他成员的冠状病毒科。我们还表明，这些刺突NTD（S-NTD）蛋白粘附在Calu 3细胞（一种人肺细胞系）上，尽管其生物学相关性尚不清楚。与中东呼吸综合征冠状病毒（MERS-CoV）在细胞进入过程中附着唾液酸的情况相反，Calu 3细胞上存在的唾液酸抑制了肉瘤病毒感染。因此，虽然Sarbecoviruses可以与其他冠状病毒类似地与细胞表面聚糖相互作用，但它们对聚糖进入的依赖与其他呼吸道冠状病毒不同，这表明Sarbecoviruses和MERS-CoV在其分歧进化期间适应了不同的细胞类型，组织或宿主。我们的发现为进一步探索Sarbecovirus聚糖结合的生物学功能提供了重要线索，并增加了我们对塑造冠状病毒尖峰进化的复杂力量的理解。重要性Sarbecoviruses的刺突N-末端结构域（S-NTD）是高度多样化的;然而，与受体结合结构域（RBD）相比，它们的功能仍然在很大程度上研究不足。在这里，我们表明，Sarbecovirus S-NTD可以在遗传学上聚集成五个分支，并在体外表现出不同水平的聚糖结合。我们还表明，与包括MERS CoV在内的一些冠状病毒不同，Calu 3（一种人肺细胞培养物）表面存在的唾液酸抑制SARS-CoV-2和其他肉瘤病毒。这些结果表明，虽然聚糖结合可能是不同冠状病毒家族中保守的祖先特征，但感染期间的功能结果可能不同，反映了不同的病毒进化。我们的研究结果扩展了我们对S-NTD在不同Sarbecoviruses中的生物学功能的了解，并提供了对冠状病毒刺突进化历史的见解。
The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to other members of the Coronaviridae family. We also show that these spike NTD (S-NTD) proteins adhere to Calu3 cells, a human lung cell line, although the biological relevance of this is unclear. In contrast to what has been shown for Middle East respiratory syndrome coronavirus (MERS-CoV), which attaches sialic acids during cell entry, sialic acids present on Calu3 cells inhibited sarbecovirus infection. Therefore, while sarbecoviruses can interact with cell surface glycans similarly to other coronaviruses, their reliance on glycans for entry is different from that of other respiratory coronaviruses, suggesting sarbecoviruses and MERS-CoV have adapted to different cell types, tissues, or hosts during their divergent evolution. Our findings provide important clues for further exploring the biological functions of sarbecovirus glycan binding and adds to our growing understanding of the complex forces that shape coronavirus spike evolution. IMPORTANCE Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. We also show that, unlike some coronaviruses, including MERS-CoV, sialic acids present on the surface of Calu3, a human lung cell culture, inhibit SARS-CoV-2 and other sarbecoviruses. These results suggest that while glycan binding might be an ancestral trait conserved across different coronavirus families, the functional outcome during infection can vary, reflecting divergent viral evolution. Our results expand our knowledge on the biological functions of the S-NTD across diverse sarbecoviruses and provide insight on the evolutionary history of coronavirus spike.
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影响因子：
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