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

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外文摘要：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.

外文关键词：

coronavirus glycosylationviral fitnessadjustable infectivityco-factor usageviral evolutionconformational modulator

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

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作者单位：

CAS Key Laboratory of Infection and Immunity,National Laboratory of Macromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

University of Chinese Academy of Sciences,Beijing 100049,China

Cambridge Institute of Therapeutic Immunology &Infectious Disease(CITIID),University of Cambridge,Cambridge CB2 0AW,UK

Biomedical Pioneering Innovation Center(BIOPIC),Peking University,Beijing 100080,China

Changping Laboratory,Beijing 102206,China

Joint Graduate Program of Peking-Tsinghua-NIBS,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871,China

Peking-Tsinghua Center for Life Sciences,Tsinghua University,Beijing 100084,China

Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100006,China

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基金：

National Key Research and Development ProgramNational Key Research and Development ProgramMinistry of Science and Technology of ChinaMinistry of Science and Technology of ChinaCASNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Science Fund for Distinguished Young ScholarNSFS Innovative Research Group

项目编号：

2023YFC23060002018YFA0900801CPL-1233SRPG22-003YSBR-0101203400632325004T23944823232500481921005

出版年：

2024

DOI：

10.1093/nsr/nwae206

国家科学评论(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.11(7)