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Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through structural plasticity

National Science Review 2024年第7期11卷 80-94页

作者： 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 CAS Key Laboratory of Infection and Immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of Sciences University of Chinese Academy of Sciences Cambridge Institute of Therapeutic Immunology&Infectious Disease(CITIID) University of Cambridge Biomedical Pioneering Innovation Center(BIOPIC) Peking University Changping Laboratory Joint Graduate Program of Peking-Tsinghua-NIBS Academy for Advanced Interdisciplinary Studies Peking University Peking-Tsinghua Center for Life Sciences Tsinghua University Chinese Academy of Medical Sciences&Peking Union Medical College

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.

关键词： coronavirus glycosylation viral fitness adjustable infectivity co-factor usage viral evolution conformational modulator

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