Enterovirus 71 infection activates the NLRP3 inflammasome in myeloid cells, while viral proteases 2A and 3C reciprocally cleave NLRP3 to counteract inflammasome activation.
Demonstrates a reciprocal regulatory mechanism where EV71 activates the NLRP3 inflammasome but simultaneously uses viral proteases to cleave NLRP3 and evade the immune response.
Enterovirus 71 (EV71) is the major etiological agent of hand, foot, and mouth disease (HFMD). Early studies showed that EV71-infected patients with severe complications exhibited elevated plasma levels of IL-1β, indicating that EV71 may activate inflammasomes. Our current study demonstrates that the NLRP3 inflammasome plays a protective role against EV71 infection of mice in vivo. EV71 replication in myeloid cells results in the activation of the NLRP3 inflammasome and secretion of IL-1β. Conversely, EV71 counteracts inflammasome activation through cleavage of NLRP3 by viral proteases 2A and 3C, which cleave NLRP3 protein at the G493-L494 or Q225-G226 junction, respectively. Moreover, EV71 3C interacts with NLRP3 and inhibits IL-1β secretion when expressed in mammalian cells. These results thus reveal a set of reciprocal regulations between enterovirus 71 and the NLRP3 inflammasome.
Wang et al. (Thu,) conducted a other in Enterovirus 71 (EV71) infection. Enterovirus 71 (EV71) infection was evaluated on NLRP3 inflammasome activation and IL-1β secretion. Enterovirus 71 infection activates the NLRP3 inflammasome in myeloid cells, while viral proteases 2A and 3C reciprocally cleave NLRP3 to counteract inflammasome activation.