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Published on: June 14, 2022
SARS-CoV-2 Spike Does Not Possess Intrinsic Superantigen-like Inflammatory Activity
Carola Amormino1,2, Valentina Tedeschi1, Giorgia Paldino1
1Department of Biology and Biotechnology Charles Darwin, Sapienza University, 00185 Rome, Italy.
Abstract:
Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory disease occurring several weeks after SARS-CoV-2 infection. The clinical similarities between MIS-C and the toxic shock syndrome, together with the preferential expansion of T cells with a T-cell receptor variable β chain (TCRVβ) skewing, suggested a superantigen theory of MIS-C. For instance, recent in silico modelling evidenced the presence of a highly conserved motif within SARS-CoV-2 spike protein similar in structure to the superantigenic fragment of staphylococcal enterotoxin B (SEB). However, experimental data on the superantigenic activity of the SARS-CoV-2 spike have not yet been provided. Here, we assessed the superantigenic activity of the SARS-CoV-2 spike by analysing inflammatory cytokine production in both Jurkat cells and the peripheral blood CD4+ T cells stimulated with the SARS-CoV-2 spike or SEB as a control. We found that, unlike SEB, the SARS-CoV-2 spike does not exhibit an intrinsic superantigen-like activity.
Insights
The SARS-CoV-2 spike protein does not exhibit superantigen activity, contrary to theories suggesting it causes Multisystem Inflammatory Syndrome in Children (MIS-C). This study found no evidence of the spike protein triggering hyperinflammation like bacterial superantigens.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare hyperinflammatory condition following SARS-CoV-2 infection.
- Clinical parallels with toxic shock syndrome and T-cell receptor (TCRVβ) skewing suggested a superantigen mechanism for MIS-C.
- In silico analysis indicated a potential superantigenic motif in the SARS-CoV-2 spike protein, similar to staphylococcal enterotoxin B (SEB).
Purpose of the Study:
- To experimentally investigate the superantigenic activity of the SARS-CoV-2 spike protein.
- To compare the inflammatory cytokine production induced by the SARS-CoV-2 spike protein versus a known superantigen (SEB).
Main Methods:
- Assessed superantigenic activity by analyzing inflammatory cytokine production.
- Utilized Jurkat cells and peripheral blood CD4+ T cells.
- Stimulated cells with either the SARS-CoV-2 spike protein or SEB as a control.
Main Results:
- The SARS-CoV-2 spike protein did not induce inflammatory cytokine production in stimulated cells.
- SEB, used as a positive control, demonstrated superantigenic activity.
- No intrinsic superantigen-like activity was detected for the SARS-CoV-2 spike protein.
Conclusions:
- The SARS-CoV-2 spike protein does not possess intrinsic superantigen-like activity.
- This finding challenges the superantigen theory for the pathogenesis of MIS-C.
- Further research is needed to elucidate the mechanisms underlying MIS-C.
