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bioRxiv · 10.1101/2024.05.16.594569

Interleukin-1 prevents SARS-CoV-2-induced membrane fusion to restrict viral transmission via induction of actin bundles

Zheng, X.·Yu, S.·Zhou, Y.·Yu, K.·Gao, Y.·Chen, M.·Duan, D.·Li, Y.·Cui, X.·Mou, J.·Yang, Y.·Wang, X.·Jiu, Y.·Zhao, J.·Meng, G.
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Abstract

Innate immune responses triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection play pivotal roles in the pathogenesis of COVID-19, while host factors including pro-inflammatory cytokines are critical for viral containment. By utilizing quantitative and qualitative models, we discovered that soluble factors secreted by human monocytes potently inhibit SARS-CoV-2-induced cell-cell fusion in viral-infected cells. Through cytokine screening, we identified that interleukin-1{beta} (IL-1{beta}), a key mediator of inflammation, inhibits syncytia formation mediated by various SARS-CoV-2 strains. Mechanistically, IL-1{beta} activates RhoA/ROCK signaling through a non-canonical IL-1 receptor-dependent pathway, which drives the enrichment of actin bundles at the cell-cell junctions, thus prevents syncytia formation. Notably, in vivo infection experiments in mice confirms that IL-1{beta} significantly restricted SARS-CoV-2 spreading in the lung epithelia. Together, by revealing the function and underlying mechanism of IL-1{beta} on SARS-CoV-2-induced cell-cell fusion, our study highlights an unprecedented antiviral function for cytokines during viral infection.

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Zheng, X., Yu, S., Zhou, Y., Yu, K., Gao, Y., Chen, M., Duan, D., Li, Y., Cui, X., Mou, J., Yang, Y., Wang, X., Jiu, Y., Zhao, J., Meng, G.. 2024-05-17. Interleukin-1 prevents SARS-CoV-2-induced membrane fusion to restrict viral transmission via induction of actin bundles. https://doi.org/10.1101/2024.05.16.594569

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