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

• Published in: Cytokine (Philadelphia, Pa.) Vol. 178; p. 156592
• Main Authors: Kawata, Daisuke, Iwai, Hideyuki, Oba, Seiya, Komiya, Yoji, Koike, Ryuji, Miyamoto, Sho, Kanno, Takayuki, Ainai, Akira, Suzuki, Tadaki, Hosoya, Tadashi, Yasuda, Shinsuke
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2024
• Subjects: Ataxia Telangiectasia Mutated Proteins; COVID-19; Humans; Inflammatory cytokine; Monocyte-derived macrophage; NF-κB; SARS-CoV-2; Spike Glycoprotein, Coronavirus - genetics; Spike protein (S-protein); Variants of concern (VOCs); Monocyte-derived macrophage; NF-κB; SARS-CoV-2; Variants of concern (VOCs); Inflammatory cytokine; Spike protein (S-protein)
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2024.156592

SARS-CoV-2 spike proteins (S-proteins) possess pro-inflammatory abilities via the NF-κB pathway in human macrophages. The production of NF-κB-responsive cytokines by macrophages in response to S-proteins varies among SARS-CoV-2 strains. A similar trend of immunostimulatory abilities was observed between SARS-CoV-2 S-proteins and live virus particles. S-protein mutations could be related to the diversity in macrophage activation caused by various SARS-CoV-2 strains. [Display omitted] •SARS-CoV-2 S-proteins possess pro-inflammatory abilities via the NF-κB pathway in human macrophages.•The production of NF-κB-responsive cytokines by macrophages in response to S-proteins varies among SARS-CoV-2 strains.•A similar trend of immunostimulatory abilities was observed between SARS-CoV-2 S-proteins and live virus particles.•S-protein mutations may be one of the factors for the variations in macrophage activation and severity rates in COVID-19 caused by each variant of concern (VOC) The severity of COVID-19 has been reported to differ among SARS-CoV-2 mutant variants. The overactivation of macrophages is involved in severe COVID-19, yet the effects of SARS-CoV-2 mutations on macrophages remain poorly understood. To clarify the effects, we examined whether mutations of spike proteins (S-proteins) affect macrophage activation. CD14+ monocyte-derived macrophages were stimulated with the recombinant S-protein of the wild-type, Delta, and Omicron strains or live viral particles of individual strains. Regarding IL-6 and TNF-α, Delta or Omicron S-protein had stronger or weaker pro‑inflammatory ability, respectively, than the wild-type. Similar trends were observed between S-proteins and viral particles. S-protein mutations could be related to the diversity in macrophage activation and severity rates in COVID-19 caused by various SARS-CoV-2 strains.