DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation

Abstract

The NLRP3 inflammasome plays a major role in innate immune responses by activating caspase-1, resulting in secretion of IL-1β and inflammatory pathologic responses. Viral RNA can induce NLRP3 inflammasome activation. However, none of the components of NLRP3 inflammasome has the ability to bind viral RNA. Therefore, it had been proposed that there might have been some unidentified cytosolic RNA sensors that could bind viral RNA and NLRP3 to initiate NLRP3 inflammasome activation. In this study, DDX19A, a member of the DEAD/H-box protein family, was identified as a novel component of NLRP3 inflammasome using arterivirus infection as a model. We found that DDX19A interacted with viral RNA and NLRP3. Knockdown of DDX19A expression efficiently inhibited procaspase-1 cleavage and IL-1β secretion in porcine reproductive and respiration syndrome virus (PRRSV)-infected or PRRSV RNA-stimulated primary porcine alveolar macrophages. Overall, DDX19A was identified as a novel cytosolic RNA sensor that bridged PRRSV RNA and NLRP3 to activate NLRP3 inflammasome.