Vulnerabilities in coronavirus glycan shields despite extensive glycosylation
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Abstract
Severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses (CoVs) are zoonotic pathogens with high fatality rates and pandemic potential. Vaccine development focuses on the principal target of the neutralizing humoral immune response, the spike (S) glycoprotein. Coronavirus S proteins are extensively glycosylated, encoding around 66–87 N-linked glycosylation sites per trimeric spike. Here, we reveal a specific area of high glycan density on MERS S that results in the formation of oligomannose-type glycan clusters, which were absent on SARS and HKU1 CoVs. We provide a comparison of the global glycan density of coronavirus spikes with other viral proteins including HIV-1 envelope, Lassa virus glycoprotein complex, and influenza hemagglutinin, where glycosylation plays a known role in shielding immunogenic epitopes. Overall, our data reveal how organisation of glycosylation across class I viral fusion proteins influence not only individual glycan compositions but also the immunological pressure across the protein surface.
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SciScore for 10.1101/2020.02.20.957472: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources H3N2 Victoria 2011 hemagglutinin was also expressed in the HEK 293F cells. HEK 293Fsuggested: RRID:CVCL_6642)Software and Algorithms Sentences Resources Data acquisition and processing were carried out using MassLynx v4.11 and Driftscope version 2.8 software (Waters) MassLynxsuggested: (MassLynx , RRID:SCR_014271)Empirical distributions of time-scaled phylogenies were obtained by combining (after the removal of burnin) the posterior tree distributions from the separate runs, which were subsequently used to estimate dN/dS ratios using the renaissance counting approach 79,80 implemented … SciScore for 10.1101/2020.02.20.957472: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Experimental Models: Cell Lines Sentences Resources H3N2 Victoria 2011 hemagglutinin was also expressed in the HEK 293F cells. HEK 293Fsuggested: RRID:CVCL_6642)Software and Algorithms Sentences Resources Data acquisition and processing were carried out using MassLynx v4.11 and Driftscope version 2.8 software (Waters) MassLynxsuggested: (MassLynx , RRID:SCR_014271)Empirical distributions of time-scaled phylogenies were obtained by combining (after the removal of burnin) the posterior tree distributions from the separate runs, which were subsequently used to estimate dN/dS ratios using the renaissance counting approach 79,80 implemented in BEAST v 1.8.4. BEASTsuggested: (BEAST, RRID:SCR_010228)Single-particle data processing was performed using CryoSparc v. CryoSparcsuggested: (cryoSPARC, RRID:SCR_016501)283 and Relion v.384. 3D variability analyses were performed in SPARX85,86. Relionsuggested: (RELION, RRID:SCR_016274)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
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- No protocol registration statement was detected.
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