Epigenetic glycosylation of SARS-CoV-2 impact viral infection through DC&L-SIGN receptors

Lei Guo,Yan Liang,Heng Li,Huiwen Zheng,Zening Yang,Yanli Chen,Xin Zhao,Jing Li,Binxiang Li,Haijing Shi,Ming Sun,Longding Liu

doi:10.1016/j.isci.2021.103426

Abstract

SummaryGlycosylation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein mediates viral entry and immune escape. While glycan site is determined by viral genetic code, glycosylation is completely dependent on host cell post-translational modification. Here, by producing SARS-CoV-2 virions from various host cell lines, viruses of different origins with diverse spike protein glycan patterns were revealed. Binding affinities to C-type lectin receptors (CLRs) DC&L-SIGN differed in the different glycan pattern virions. Although none of the CLRs supported viral productive infection, viral trans&cis-infection mediated by the CLRs were substantially changed among the different virions. Specifically, trans&cis-infection of virions with a high-mannose structure (Man5GlcNAc2) at the N1098 glycan site of the spike postfusion trimer were markedly enhanced. Considering L-SIGN co-expression with ACE2 on respiratory tract cells, our work underlines viral epigenetic glycosylation in authentic viral infection and highlights the attachment co-receptor role of DC&L-SIGN in SARS-CoV-2 infection and prevention.

Highlights

Over one and a half years after its outbreak, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains ongoing
Binding affinities to C-type lectin receptors (CLRs) DC&L-SIGN differed in the different glycan pattern virions
DC- and L-SIGN bind to SARS-CoV-2 S protein via glycans but cannot directly support SARSCoV-2 proliferation Affinities of S glycoprotein and DC/L-SIGN were measured by microscale thermophoresis (MST) assay and the results showed that both DC-SIGN and L-SIGN interact with recombinant S protein with a relatively lower affinity (Kd, 28.8 nM, 43.7 nM, respectively) than that of the ACE2 receptor (Kd, 3.04 nM) (Figures 1A, 1B, and 1C)

Summary

Introduction

Over one and a half years after its outbreak, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains ongoing. The viral surface trimeric spike (S) glycoprotein binds to its receptor ACE2, and after binding the S trimer undergoes proteolytic cleavage and conformational change from the prefusion to postfusion form which triggers membrane fusion and delivers the viral genome into the cytosol to initiate replication (Lan et al, 2020). S undergoes extensive glycosylation per protomer and glycans present on both prefusion and postfusion trimers of viral surface (Cai et al, 2020; Watanabe et al, 2020; Yao et al, 2020; Zhao et al, 2020). Heavy glycosylation of viral entry protein is considered a way of virus immune escape by forming a glycan shield (Watanabe et al, 2019). Glycan presented on S protein has been suggested to support S-ACE2 binding in conformation and mediate infection as ligands for lectin receptor binding (Casalino et al, 2020; Evans and Liu, 2021)

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