Zhang Liping, Mann Matthew, Syed Zulfeqhar, Reynolds Hayley M, Tian E, Samara Nadine L, Zeldin Darryl C, Tabak Lawrence A, Ten Hagen Kelly G
Developmental Glycobiology Section, NIDCR, National Institutes of Health, Bethesda, Maryland 20892-4370.
Section on Biological Chemistry, NIDCR, National Institutes of Health, Bethesda, Maryland 20892-4370.
bioRxiv. 2021 Feb 5:2021.02.05.429982. doi: 10.1101/2021.02.05.429982.
The SARS-CoV-2 coronavirus responsible for the global pandemic contains a unique furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation. Here, we show that O-glycosylation near the furin cleavage site is mediated by specific members of the GALNT enzyme family and is dependent on the novel proline at position 681 (P681). We further demonstrate that O-glycosylation of S decreases furin cleavage. 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 O-glycosylation may influence viral infectivity/tropism by modulating furin cleavage of S and provide mechanistic insight into the potential role of P681 mutations in the recently identified, highly transmissible B.1.1.7 variant.
引发全球大流行的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）在刺突蛋白（S）中含有一个独特的弗林蛋白酶切割位点，该位点可增加病毒的感染性和多核体形成。在此，我们表明弗林蛋白酶切割位点附近的O-糖基化由GALNT酶家族的特定成员介导，并且依赖于第681位（P681）的新型脯氨酸。我们进一步证明S的O-糖基化会降低弗林蛋白酶切割。最后，我们表明能够对S进行糖基化的GALNT家族成员在作为SARS-CoV-2感染靶标的人类呼吸道细胞中表达。我们的结果表明，O-糖基化可能通过调节S的弗林蛋白酶切割来影响病毒感染性/嗜性，并为最近鉴定出的高传播性B.1.1.7变体中P681突变的潜在作用提供了机制性见解。
