tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2021 Nov 23;118(47):e2109905118.
doi: 10.1073/pnas.2109905118.
Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation
Liping Zhang[SUP] 1 [/SUP], Matthew Mann[SUP] 2 [/SUP], Zulfeqhar A Syed[SUP] 1 [/SUP], Hayley M Reynolds[SUP] 1 [/SUP], E Tian[SUP] 1 [/SUP], Nadine L Samara[SUP] 3 [/SUP], Darryl C Zeldin[SUP] 4 [/SUP], Lawrence A Tabak[SUP] 2 [/SUP], Kelly G Ten Hagen[SUP] 5 [/SUP]
Affiliations
Abstract
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.
Keywords: COVID-19; O-; SARS-CoV-2; furin; glycosylation; spike.
. 2021 Nov 23;118(47):e2109905118.
doi: 10.1073/pnas.2109905118.
Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation
Liping Zhang[SUP] 1 [/SUP], Matthew Mann[SUP] 2 [/SUP], Zulfeqhar A Syed[SUP] 1 [/SUP], Hayley M Reynolds[SUP] 1 [/SUP], E Tian[SUP] 1 [/SUP], Nadine L Samara[SUP] 3 [/SUP], Darryl C Zeldin[SUP] 4 [/SUP], Lawrence A Tabak[SUP] 2 [/SUP], Kelly G Ten Hagen[SUP] 5 [/SUP]
Affiliations
- PMID: 34732583
- DOI: 10.1073/pnas.2109905118
Abstract
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.
Keywords: COVID-19; O-; SARS-CoV-2; furin; glycosylation; spike.