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Diverse pro-inflammatory ability of mutated spike protein derived from variant strains of SARS-CoV-2

Daisuke Kawata1, Hideyuki Iwai1, Seiya Oba1

  • 1Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Cytokine
|April 4, 2024
PubMed

Insights

SARS-CoV-2 mutations in spike proteins affect macrophage activation, influencing COVID-19 severity. Delta and Omicron variants show distinct pro-inflammatory responses compared to the wild-type, impacting disease outcomes.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • COVID-19 severity varies significantly between SARS-CoV-2 variants.
  • Macrophage overactivation is a key factor in severe COVID-19.
  • The impact of SARS-CoV-2 mutations on macrophage behavior is not well understood.

Purpose of the Study:

  • To investigate how SARS-CoV-2 spike protein mutations influence macrophage activation.
  • To determine if specific variants (Delta, Omicron) exhibit different effects on macrophages compared to the wild-type virus.

Main Methods:

  • Utilized CD14+ monocyte-derived macrophages.
  • Stimulated macrophages with recombinant spike proteins (wild-type, Delta, Omicron) and live viral particles.
  • Measured pro-inflammatory cytokine (IL-6, TNF-α) production.

Main Results:

  • Delta and Omicron spike proteins demonstrated stronger and weaker pro-inflammatory abilities, respectively, compared to the wild-type.
  • Similar trends in macrophage activation were observed when using live viral particles.
  • Spike protein mutations correlate with differential macrophage activation patterns.

Conclusions:

  • SARS-CoV-2 spike protein mutations play a role in modulating macrophage activation.
  • These variations in macrophage response may contribute to the differing severity rates observed across COVID-19 variants.
Keywords:
Inflammatory cytokineMonocyte-derived macrophageNF-κBSARS-CoV-2Spike protein (S-protein)Variants of concern (VOCs)

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