SARS-CoV-2 virus-like particle variants alpha and delta mimic the native viruses in their differential inflammasome activating potential

In this study, we focused on the capacity of SARS-CoV-2 Alpha and Delta variants to activate the NLRP3 inflammasome. We compared the macrophage activation, particularly the inflammasome formation, using Alpha- and Delta-spike virus-like particles (VLPs). We found that VLPs of both variants activated the inflammasome even without a priming step. Delta-spike VLPs had a significantly stronger effect on triggering pyroptosis and inflammasome assembly in THP-1 macrophages than did Alfa-spike VLPs. Cells treated with Delta VLPs showed greater cleavage of caspase-1 and IL-1β release. Furthermore, Delta VLPs induced stronger cytokine secretion from macrophages and caused essential impairment of mitochondrial respiration in comparison to Alpha VLPs. Additionally, infection of primary human monocyte-derived macrophages with the SARS-CoV-2 variants confirmed the observations in VLPs. Collectively, we revealed that SARS-CoV-2 Delta had a greater impact on the inflammasome activation, cell death and mitochondrial respiration in macrophages than did the Alpha variant. Importantly, the differential response to the SARS-CoV-2 variants can influence the efficacy of therapies targeting the host's innate immunity.PMID:38453031 | DOI:10.1016/j.antiviral.2024.105857

Source: Antiviral Research - March 7, 2024 Category: Virology Authors: Magdalena Bandyszewska Magdalena Ambro żek-Latecka Gra żyna Hoser Ma łgorzata Grzanka Franziska Hornung Stefanie Deinhardt-Emmer Tomasz Skirecki Source Type: research