tetano
Editor, Senior Moderator
Elife
. 2025 Feb 12:13:RP98593.
doi: 10.7554/eLife.98593. Interleukin-1 prevents SARS-CoV-2-induced membrane fusion to restrict viral transmission via induction of actin bundles
Xu Zheng[SUP] #[/SUP][SUP] 1 [/SUP], Shi Yu[SUP] #[/SUP][SUP] 1 [/SUP], Yanqiu Zhou[SUP] #[/SUP][SUP] 2 [/SUP], Kuai Yu[SUP] #[/SUP][SUP] 3 [/SUP], Yuhui Gao[SUP] 1 [/SUP], Mengdan Chen[SUP] 1 [/SUP], Dong Duan[SUP] 1 4 [/SUP], Yunyi Li[SUP] 2 [/SUP], Xiaoxian Cui[SUP] 2 [/SUP], Jiabin Mou[SUP] 2 [/SUP], Yuying Yang[SUP] 2 [/SUP], Xun Wang[SUP] 5 [/SUP], Min Chen[SUP] 2 [/SUP], Yaming Jiu[SUP] 1 [/SUP], Jincun Zhao[SUP] 3 [/SUP], Guangxun Meng[SUP] 1 4 [/SUP]
Affiliations
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 proinflammatory 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-1β (IL-1β), a key mediator of inflammation, inhibits syncytia formation mediated by various SARS-CoV-2 strains. Mechanistically, IL-1β 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 confirmed that IL-1β significantly restricted SARS-CoV-2 spread in the lung epithelium. Together, by revealing the function and underlying mechanism of IL-1β on SARS-CoV-2-induced cell-cell fusion, our study highlights an unprecedented antiviral function for cytokines during viral infection.
Keywords: SARS-CoV-2; actin bundle; cell-cell fusion; human; immunology; infectious disease; inflammation; innate immune cell; interlukin-1; microbiology; mouse.
. 2025 Feb 12:13:RP98593.
doi: 10.7554/eLife.98593. Interleukin-1 prevents SARS-CoV-2-induced membrane fusion to restrict viral transmission via induction of actin bundles
Xu Zheng[SUP] #[/SUP][SUP] 1 [/SUP], Shi Yu[SUP] #[/SUP][SUP] 1 [/SUP], Yanqiu Zhou[SUP] #[/SUP][SUP] 2 [/SUP], Kuai Yu[SUP] #[/SUP][SUP] 3 [/SUP], Yuhui Gao[SUP] 1 [/SUP], Mengdan Chen[SUP] 1 [/SUP], Dong Duan[SUP] 1 4 [/SUP], Yunyi Li[SUP] 2 [/SUP], Xiaoxian Cui[SUP] 2 [/SUP], Jiabin Mou[SUP] 2 [/SUP], Yuying Yang[SUP] 2 [/SUP], Xun Wang[SUP] 5 [/SUP], Min Chen[SUP] 2 [/SUP], Yaming Jiu[SUP] 1 [/SUP], Jincun Zhao[SUP] 3 [/SUP], Guangxun Meng[SUP] 1 4 [/SUP]
Affiliations
- PMID: 39937682
- DOI: 10.7554/eLife.98593
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 proinflammatory 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-1β (IL-1β), a key mediator of inflammation, inhibits syncytia formation mediated by various SARS-CoV-2 strains. Mechanistically, IL-1β 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 confirmed that IL-1β significantly restricted SARS-CoV-2 spread in the lung epithelium. Together, by revealing the function and underlying mechanism of IL-1β on SARS-CoV-2-induced cell-cell fusion, our study highlights an unprecedented antiviral function for cytokines during viral infection.
Keywords: SARS-CoV-2; actin bundle; cell-cell fusion; human; immunology; infectious disease; inflammation; innate immune cell; interlukin-1; microbiology; mouse.