SARS-CoV-2 spike protein interacts with multiple innate immune receptors
cell biology immunology/immunity inflammation molecular biology
Authors:Gao et al
Journal/ Pre-Print:bioRxiv
Tags: Cell Biology, Immunology/Immunity, Inflammation, Molecular biology
Research Highlights
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Identification of C-type lectin receptors that bind SARS-CoV-2 S protein in a glycan-dependent manner
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Expression levels of DC-SIGN and MGL on macrophages and dendritic cells increase in severe COVID-19 patients
Summary
Gao et al aimed to characterise the connection between the glycosylation pattern of the spike protein S and recognition by glycan-binding pattern recognition receptors. They identified C-type lectin receptors (CLRs) DC-SIGN, L-SIGN, MR and MGL as binding to SARS-CoV-2 via different glycans. DC-SIGN, MR and MGL had a strong binding affinity for S protein. By glycomics it was confirmed that the glycans on SARS-CoV-2 could serve as ligands for the CRLs mentioned above. Furthermore, by interrogating existing scRNA-seq data of COVID-19 patients, they confirmed expression of CRLs in resident immune cells and an increase in expression levels of DC-SIGN and MGL in severe COVID-19 patients. By blocking CRL receptors, SARS-CoV-2 spread might be attenuated and immune cell hyperactivation limited.
Impact for SARS-CoV2/COVID19 research efforts
Understand the virology and/or cell biology of SARS-CoV2/COVID19: looking at the glycosylation pattern of SARS-CoV-2 and its recognition by innate immune receptors
Study Type
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In silico study / bioinformatics study
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In vitro study
Strengths and limitations of the paper
Novelty: SARS-CoV-2 is recognised in a glycan-dependent manner by various innate immune receptors, new O-glycosylation sites discovered
Standing in the field:Glycosylation pattern of full SARS-CoV-2 published previously, connection with innate immune receptors not uncovered
Appropriate statistics: Statistics not applicable, but in the one case where they applied it, they did not describe the test used
Viral model used:Recombinant full-length S-protein produced by HEK293 cells
Translatability:Recognition and internalisation by innate immune cells as an alternative interaction route of SARS-CoV-2, leading to pathological cytokine storm, potential new therapeutic avenues (blocking these receptors)
Main limitations: In vitro study, might not reflect mucosal environment (especially as Vero E6 cells are used for SARS-CoV-2 internalisation), ACE2 still has a much higher affinity for SARS-CoV-2 than the CRLs, only part of the virus used (whereas with complete virus there could be masking of some of the glycosylation sites), results of SARS-Cov-2 binding (pathway activation/cytokine secretion) only by correlation with scRNA-seq dataset