Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through structural plasticity
Pan Liu, Can Yue, Bo Meng, Tianhe Xiao, Sijie Yang, Shuo Liu, Fanchong Jian, Qianhui Zhu, Yuanling Yu, Yanyan Ren, Peng Wang, Yixin Li, Jinyue Wang, Xin Mao, Fei Shao, Youchun Wang, Ravindra Kumar Gupta, Yunlong Cao, Xiangxi Wang
Abstract
Selective pressures have given rise to a number of SARS-CoV-2 variants during the prolonged course of the COVID-19 pandemic. Recently evolved variants differ from ancestors in additional glycosylation within the spike protein receptor-binding domain (RBD). Details of how the acquisition of glycosylation impacts viral fitness and human adaptation are not clearly understood. Here, we dissected the role of N354-linked glycosylation, acquired by BA.2.86 sub-lineages, as a RBD conformational control element in attenuating viral infectivity. The reduced infectivity is recovered in the presence of heparin sulfate, which targets the ‘N354 pocket’ to ease restrictions of conformational transition resulting in a ‘RBD-up’ state, thereby conferring an adjustable infectivity. Furthermore, N354 glycosylation improved spike cleavage and cell–cell fusion, and in particular escaped one subset of ADCC antibodies. Together with reduced immunogenicity in hybrid immunity background, these indicate a single spike amino acid glycosylation event provides selective advantage in humans through multiple mechanisms.
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Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through structural plasticity, NSR, 14 Jun 2024
National Science Review, 14 June, 2024, DOI：https://doi.org/10.1093/nsr/nwae206
Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through structural plasticity
Pan Liu, Can Yue, Bo Meng, Tianhe Xiao, Sijie Yang, Shuo Liu, Fanchong Jian, Qianhui Zhu, Yuanling Yu, Yanyan Ren, Peng Wang, Yixin Li, Jinyue Wang, Xin Mao, Fei Shao, Youchun Wang, Ravindra Kumar Gupta, Yunlong Cao, Xiangxi Wang
Abstract
Selective pressures have given rise to a number of SARS-CoV-2 variants during the prolonged course of the COVID-19 pandemic. Recently evolved variants differ from ancestors in additional glycosylation within the spike protein receptor-binding domain (RBD). Details of how the acquisition of glycosylation impacts viral fitness and human adaptation are not clearly understood. Here, we dissected the role of N354-linked glycosylation, acquired by BA.2.86 sub-lineages, as a RBD conformational control element in attenuating viral infectivity. The reduced infectivity is recovered in the presence of heparin sulfate, which targets the ‘N354 pocket’ to ease restrictions of conformational transition resulting in a ‘RBD-up’ state, thereby conferring an adjustable infectivity. Furthermore, N354 glycosylation improved spike cleavage and cell–cell fusion, and in particular escaped one subset of ADCC antibodies. Together with reduced immunogenicity in hybrid immunity background, these indicate a single spike amino acid glycosylation event provides selective advantage in humans through multiple mechanisms.
文章链接：https://academic.oup.com/nsr/article/11/7/nwae206/7693733