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Protective effects of the NLRP3 inflammasome against infectious bursal disease virus replication in DF-1 cells

Inflammatory responses are an important part of the innate immune response during viral infection. Various inflammasome complexes have been identified. The pyrin domain-containing 3 (NLRP3) inflammasome plays a critical role in detecting some RNA viruses, such as influenza virus. However, the effect of the NLRP3 inflammasome on infectious bursal disease virus (IBDV) replication is still unclear. Here, we report that IBDV-infection induces the transcription of NLRP3 inflammasome and IL-1β genes in the immortalized chicken embryo fibroblast cell line DF-1. Inhibition of caspase-1 by Belnacasan (VX-765) suppressed the transcription of IL-1β, reduced cell lysis, and significantly promoted IBDV replication in DF-1 cells. Furthermore, knockdown of NLRP3 by small interfering RNA promoted IBDV replication in the host cells. Thus, IBDV can induce NLRP3 inflammasome activation in DF-1 cells through a mechanism requiring viral replication, revealing a new antiviral mechanism employed by the host.

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S2228 Belnacasan (VX-765) Belnacasan (VX-765) is a potent and selective inhibitor of caspase-1 with Ki of 0.8 nM in a cell-free assay. Phase 2.

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