期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：47
DOI：10.1073/pnas.2109905118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
The novel SARS-CoV-2 coronavirus that is responsible for the global pandemic contains a unique insertion of four amino acids within the spike protein (S). Furin cleavage at this novel insertion site has been shown to increase pseudoviral infectivity and syncytia formation. Here we show that
O-glycosylation by certain GALNT family members decreases furin cleavage of S and decreases syncytia formation. Moreover, we show that P681 mutations found in the highly transmissible alpha and delta variants decrease
O-glycosylation, which increases furin cleavage and syncytia formation. Our results highlight how host-mediated
O-glycosylation may influence viral infectivity and how mutations in the recent alpha and delta variants may circumvent this.
The SARS-CoV-2 coronavirus responsible for the global pandemic contains a novel furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation in cells. Here, we show that
O-glycosylation near the furin cleavage site is mediated by members of the GALNT enzyme family, resulting in decreased furin cleavage and decreased syncytia formation. Moreover, we show that
O-glycosylation is dependent on the novel proline at position 681 (P681). Mutations of P681 seen in the highly transmissible alpha and delta variants abrogate
O-glycosylation, increase furin cleavage, and increase syncytia formation. Finally, we show that GALNT family members capable of glycosylating S are expressed in human respiratory cells that are targets for SARS-CoV-2 infection. Our results suggest that host
O-glycosylation may influence viral infectivity/tropism by modulating furin cleavage of S and provide mechanistic insight into the role of the P681 mutations found in the highly transmissible alpha and delta variants.
