Dataset Information

Spike Glycoprotein S1 Site-specific O-glycosylation: Systematic and Comparative Analysis from Eleven Variants of SARS CoV-2

ABSTRACT: In this study, we provide a comprehensive characterization of O-glycosylation in eleven variants of SARS-CoV-2 S1 subunit recombinantly expressed in HEK293 cells.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: SHERIFDEEN ONIGBINDE

LAB HEAD: Yehia Mechref

PROVIDER: PXD041282 | Pride | 2024-01-26

REPOSITORIES: Pride

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Publications

Variations in <i>O</i>-Glycosylation Patterns Influence Viral Pathogenicity, Infectivity, and Transmissibility in SARS-CoV-2 Variants.

Onigbinde Sherifdeen S Reyes Cristian D Gutierrez CDG Fowowe Mojibola M Daramola Oluwatosin O Atashi Mojgan M Bennett Andrew I AI Mechref Yehia Y

Biomolecules 20230929 10

The highly glycosylated S protein plays a vital role in host cell invasion, making it the principal target for vaccine development. Differences in mutations observed on the spike (S) protein of SARS-CoV-2 variants may result in distinct glycosylation patterns, thus influencing immunological evasion, infectivity, and transmissibility. The glycans can mask key epitopes on the S1 protein and alter its structural conformation, allowing the virus to escape the immune system. Therefore, we comprehensi ...[more]

PMID: 37892149

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Project description:The SARS-CoV-2 spike protein mediates attachment of the virus to host cell receptor and fusion between the virus and cell membrane. The S1 subunit of the spike glycoprotein (S1 protein) contains the angiotensin converting enzyme 2 (ACE2) receptor binding domain. The SARS-CoV-2 variants of concern contain mutations in the S1 subunit. The spike protein is the primary target of neutralizing antibodies generated following infection and constitutes the viral component of mRNA based COVID-19 vaccines. Therefore, in this work we assessed the effect of exposure (24 hours) of 10 nM SARS-CoV-2 recombinant S1 protein on physiologically relevant human bronchial (bro) and alveolar (alv) lung mucosa models cultured at air-liquid interface (ALI) (n=6/experimental group). Corresponding sham exposed samples served as control. The bro-ALI model was developed using primary bronchial epithelial cells and the alv-ALI model using representative type II pneumocytes. Exposure of S1 protein induced the surface expression of ACE2, toll like receptor (TLR) 2, and TLR4 in both bro-ALI and alv-ALI models. Transcript expression analysis identified 117 (bro-ALI) and 97 (alv-ALI) differentially regulated genes (p< 0.01). Pathway analysis revealed enriched terms as specific as COVID-19, interferon (IFN) signaling, influenza, Corona virus, anti-viral response in the bro-ALI. Secreted levels of Interleukin (IL) 4 and IL12 were significantly (p<0.05; non-parametric) increased whereas IL6 decreased in the bro-ALI. In case of alv-ALI, enriched terms involving p53, APRIL, tight junction, integrin kinase, IL1 signaling were identified. These terms are associated with lung fibrosis. Further, significantly (p<0.05; non-parametric) increased levels of secreted pro-inflammatory cytokines IFNγ, IL1ꞵ, IL2, IL4, IL6, IL8, IL10, IL12, IL13, and tumor necrosis factor alpha were detected in alv-ALI. Altered levels of these cytokines are also associated with lung fibrotic response. Taken together, we observed a typical anti-viral response in the bronchial model whereas a pro-fibrotic response in the alveolar model. Therefore the bro-ALI and alv-ALI models may serve as an easy and robust platform for assessing the pathogenicity of variants of concern at different lung regions.

Dataset Information

Spike Glycoprotein S1 Site-specific O-glycosylation: Systematic and Comparative Analysis from Eleven Variants of SARS CoV-2

Publications

Variations in <i>O</i>-Glycosylation Patterns Influence Viral Pathogenicity, Infectivity, and Transmissibility in SARS-CoV-2 Variants.

Similar Datasets

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