Reciprocal Regulation between Enterovirus 71 and the NLRP3 Inflammasome

Wang H, Lei X, Xiao X, Yang C, Lu W, Huang Z, Leng Q, Jin Q, He B, Meng G, & Wang J. Cell Reports (2015) 12, 42-48.

Speaker: Yi Sheng Jiang (江翊生)                                Time: 15:00~16:00, Dec. 9, 2015

Commentator: Dr. Hsiao-Sheng Liu (劉校生老師)     Place: Room 601

Abstract:

 The genome of enterovirus 71 (EV71) encodes a single polyprotein precursor, which is processed into functional proteins by virus-encoded proteases 2A and 3C. These proteases may also inhibit host immune responses by cleaving host factors. EV71-infected patients with severe complications have been shown to exhibit elevated plasma levels of IL-1β, and IL-6, suggesting that EV71 may activate inflammasome¹. In this study, the authors reported that infant mice deficient in the components of the inflammasome complex, including NLRP3, ASC, or caspase-1, exhibited more severe disease than wild-type mice when infected with EV71, indicating that the NLRP3 inflammasome plays a protective role against EV71 infection in vivo. Furthermore, EV71 replication in myeloid cells induced NLRP3 inflammasome activation. Viral proteases 2A and 3C cleaved NLRP3 at the G493-L494 and Q225-G226 junction, respectively. Thus, EV71 can antagonize inflammasome activation through cleavage of NLRP3. These results suggest that RNA and proteins from EV71 may induce inflammasome assembly at the early phase of infection. However, when the virus replicates and generates enough 3C and 2A proteases at the later phase of infection, NLRP3 may be cleaved by these two viral proteases, resulting in inhibiting inflammasome activation. Taken together, this study reveals a set of reciprocal regulations between EV71 and the NLRP3 inflammasome and identifies potential therapeutic targets for anti-EV71 treatment.

Reference:

1.     Chang LY, Hsiung CA, Lu CY, Lin TY, Huang FY, Lai YH, Chiang YP, Chiang BL, Lee CY, Huang LM. (2006) Status of cellular rather than humoral immunity is correlated with clinical outcome of enterovirus 71. Pediatr. Res. 60, 466-471.