Allen Joel D, Ivory Dylan, Ge Song Sophie, He Wan-Ting, Capozzola Tazio, Yong Peter, Burton Dennis R, Andrabi Raiees, Crispin Max
School of Biological Sciences, University of Southampton, Southampton, SO17 1BJ, UK.
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 13 92037, USA.
bioRxiv. 2022 Aug 25:2022.08.24.505118. doi: 10.1101/2022.08.24.505118.
The animal reservoirs of sarbecoviruses represent a significant risk of emergent pandemics, as evidenced by the impact of SARS-CoV-2. Vaccines remain successful at limiting severe disease and death, however the continued emergence of SARS-CoV-2 variants, together with the potential for further coronavirus zoonosis, motivates the search for pan-coronavirus vaccines that induce broadly neutralizing antibodies. This necessitates a better understanding of the glycan shields of coronaviruses, which can occlude potential antibody epitopes on spike glycoproteins. Here, we compare the structure of several sarbecovirus glycan shields. Many N-linked glycan attachment sites are shared by all sarbecoviruses, and the processing state of certain sites is highly conserved. However, there are significant differences in the processing state at several glycan sites that surround the receptor binding domain. Our studies reveal similarities and differences in the glycosylation of sarbecoviruses and show how subtle changes in the protein sequence can have pronounced impacts on the glycan shield.
正如新冠病毒(SARS-CoV-2)所造成的影响所示,沙贝病毒属的动物宿主是新出现大流行的重大风险源。疫苗在限制重症和死亡方面仍然很成功,然而,SARS-CoV-2变体的持续出现,以及进一步出现冠状病毒人畜共患病的可能性,促使人们寻找能够诱导广泛中和抗体的泛冠状病毒疫苗。这就需要更好地了解冠状病毒的聚糖屏蔽,因为它可以遮盖刺突糖蛋白上潜在的抗体表位。在此,我们比较了几种沙贝病毒聚糖屏蔽的结构。所有沙贝病毒都共享许多N-连接聚糖附着位点,并且某些位点的加工状态高度保守。然而,在围绕受体结合域的几个聚糖位点的加工状态存在显著差异。我们的研究揭示了沙贝病毒糖基化的异同,并展示了蛋白质序列中的细微变化如何对聚糖屏蔽产生显著影响。