新加坡分子和细胞生物学研究所Bruno Reversade、Franklin L. Zhong等研究人员合作发现,肠病毒3C蛋白酶激活气道上皮细胞中的人类NLRP1炎性小体。 2020年10月22日,《科学》杂志在线发表了这项成果。
Title: Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia
Author: 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 Chow, De Yun Wang, Franklin L. Zhong, Bruno Reversade
Issue&Volume: 2020/10/22
Abstract: Immune sensor proteins are critical to the function of the human innate immune system. The full repertoire of cognate triggers for human immune sensors is not fully understood. Here, we report that human NLRP1 is activated by 3C proteases (3Cpros) of enteroviruses, such as human rhinovirus (HRV). 3Cpros directly cleave human NLRP1 at a single site between Glu130 and Gly131. This cleavage triggers N-glycine–mediated degradation of the autoinhibitory NLRP1 N-terminal fragment via the cullinZER1/ZYG11B complex, which liberates the activating C-terminal fragment. Infection of primary human airway epithelial cells by live human HRV triggers NLRP1-dependent inflammasome activation and IL-18 secretion. Our findings establish 3Cpros as a pathogen-derived trigger for the human NLRP1 inflammasome and suggest that NLRP1 may contribute to inflammatory diseases of the airway.
DOI: 10.1126/science.aay2002
Source: https://science.sciencemag.org/content/early/2020/10/21/science.aay2002