Reciprocal Regulation between Enterovirus 71 and the NLRP3 Inflammasome

Cell Rep. 2015 Jul 7;12(1):42-48. doi: 10.1016/j.celrep.2015.05.047. Epub 2015 Jun 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Enterovirus A, Human / enzymology
  • Enterovirus A, Human / physiology*
  • Inflammasomes / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myeloid Cells / metabolism
  • Myeloid Cells / virology
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Protein Binding
  • Proteolysis
  • Serine Endopeptidases / metabolism
  • Viral Proteins / metabolism
  • Virus Replication


  • Carrier Proteins
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Viral Proteins
  • Serine Endopeptidases