Vimentin recognizes African swine fever virus genomic DNA and triggers inflammatory responses by activation of NLRP3 inflammasome

Abstract Previous studies have reported that African swine fever virus (ASFV) infection can induce inflammatory responses through the activation of the NLRP3 inflammasome, resulting in the release of IL-1β and the cleavage of gasdermin D. However, the mechanism by which pattern recognition receptors in target cells recognize ASFV genomic DNA (gDNA) to activate the NLRP3 inflammasome remains unclear. In this study, we demonstrate that ASFV infection and the transfection of ASFV gDNA can trigger NLRP3-dependent inflammasome activation. Additionally, vimentin was identified as a binding partner for viral gDNA and was found to interact with NLRP3, playing a role in the activation of the NLRP3 inflammasome. Furthermore, we discovered that the knockdown of endogenous vimentin expression inhibited NLRP3 inflammasome activation, leading to a reduction in caspase-1 activation and IL-1β secretion in ASFV-infected or viral DNA–stimulated porcine alveolar macrophages. Our findings reveal a mechanism involving the interaction between vimentin and viral gDNA that mediates the activation of the NLRP3 inflammasome during ASFV infection.