刺突S2结构域n -糖基化在冠状病毒中的保守作用。

Qi Yang, Anju Kelkar, Balaji Manicassamy, Sriram Neelamegham
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引用次数: 0

摘要

除了作为免疫屏障外,SARS-CoV-2的n -聚糖对病毒的生命周期也至关重要。由于刺突的S2亚基在冠状病毒中高度保守,我们确定了位于N1098-N1194之间的S2上的5个“茎n聚糖”的功能意义。对31个Asn-to-Gln突变体、冠状病毒样颗粒和单循环病毒复制子进行了研究。茎n -聚糖的缺失增强了三聚体穗S1的脱落,减少了ACE2的结合,并破坏了合胞体的形成。当三个或更多的n -聚糖缺失时,细胞表面的刺突表达和病毒粒子的掺入都减少了。在删除N1098聚糖和其他糖基修饰后,病毒进入功能逐渐丧失。除SARS-CoV-2外,在SARS-CoV和MERS-CoV刺突中删除干n聚糖也可以阻止病毒进入靶细胞。这些数据表明,茎n -聚糖具有多种功能作用,并且这些复杂碳水化合物在人类冠状病毒中具有进化上的保守特性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Conserved role of spike S2 domain N-glycosylation across betacoronaviruses.

Besides acting as an immunological shield, the N-glycans of SARS-CoV-2 are also critical for viral life cycle. As the S2 subunit of spike is highly conserved across betacoronaviruses, we determined the functional significance of the five 'stem N-glycans' located in S2 between N1098-N1194. Studies were performed with 31 Asn-to-Gln mutants, betacoronavirus virus-like particles and single-cycle viral replicons. Deletions of stem N-glycans enhanced S1 shedding from trimeric spike, reduced ACE2 binding and abolished syncytia formation. When three or more N-glycans were deleted, spike expression on cell surface and incorporation into virions was both reduced. Viral entry function was progressively lost upon deleting the N1098 glycan in combination with additional glycosite modifications. In addition to SARS-CoV-2, deleting stem N-glycans in SARS-CoV and MERS-CoV spike also prevented viral entry into target cells. These data suggest multiple functional roles for the stem N-glycans, and evolutionarily conserved properties for these complex carbohydrates across human betacoronaviruses.

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