title: Reciprocal Regulation between Enterovirus 71 and the NLRP3 Inflammasome.
abstract: 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.
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Wang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Lei
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Lu
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Leng
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: gxmeng@sibs.ac.cn.
authors.forename: Guangxun
authors.initials: G
authors.lastname: Meng
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China. Electronic address: wangjw28@163.com.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D029821:Enterovirus A, Human / Q000201:enzymology / Q000502:physiology*; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism / Q000821:virology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011485:Protein Binding; D059748:Proteolysis; D012697:Serine Endopeptidases / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D014764:Viral Proteins; D012697:Serine Endopeptidases