Cell Reports
Volume 12, Issue 1, 7 July 2015, Pages 42-48
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Reciprocal Regulation between Enterovirus 71 and the NLRP3 Inflammasome

https://doi.org/10.1016/j.celrep.2015.05.047Get rights and content
Under a Creative Commons license
open access

Highlights

  • The NLRP3 inflammasome plays a protective role against EV71 infection in vivo

  • EV71 replication in myeloid cells induces NLRP3 inflammasome activation

  • EV71 antagonizes inflammasome activation through cleavage of NLRP3 by 2A and 3C

Summary

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.

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Co-first author