Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia

• DOI: 10.1126/science.aay2002
• Publication Date: 2020-10-22T23:11:15Z
• Authors: Kim S. Robinson; Daniel Eng Thiam Teo; Kai Sen Tan; Gee Ann Toh; Hsiao Hui Ong; Chrissie Kaishi Lim; Kenneth Lay; Bijin Veonice Au; Tian Sheng Lew; Justin Jang Hann Chu; Vincent Tak Kwong...; De Yun Wang; Franklin L. Zhong; Bruno Reversade
• Keywords: NLRP1; AIM2

Immune sensor proteins are critical to the function of human innate immune system. The full repertoire cognate triggers for sensors is not fully understood. Here, we report that NACHT, LRR, and PYD domains-containing protein 1 (NLRP1) activated by 3C proteases (3Cpros) enteroviruses, such as rhinovirus (HRV). 3Cpros directly cleave NLRP1 at a single site between Glu130 Gly131 This cleavage N-glycine-mediated degradation autoinhibitory N-terminal fragment via cullinZER1/ZYG11B complex, which liberates activating C-terminal fragment. Infection primary airway epithelial cells live HRV NLRP1-dependent inflammasome activation interleukin-18 secretion. Our findings establish pathogen-derived trigger suggest may contribute inflammatory diseases airway.