NLRP12 Senses the SARS-CoV-2 Membrane Protein and Promotes an Inflammatory Response

Li, Xingyu1,2,3; Zhou, Guangde1; Sun, Xingzi1,2; Qu, Siying2; Lai, Hongzhi4; Wu, Yongjian2; Li, Dechang5; Liu, Lei1; Zhang, Guoliang1; Yang, Jingwen6; Huang, Xi1,2,3,7

2023-11-01

10.1093/infdis/jiad458

JOURNAL OF INFECTIOUS DISEASES   影响因子和分区

0022-1899

1537-6613

["COVID-19 is an acute respiratory disorder that is caused by SARS-CoV-2, in which excessive systemic inflammation is associated with adverse patient clinical outcomes. Here, we observed elevated expression levels of NLRP12 (nucleotide-binding leucine-rich repeat-containing receptor 12) in human peripheral monocytes and lung tissue during infection with SARS-CoV-2. Co-immunoprecipitation analysis revealed that NLRP12 directly interacted with the M protein through its leucine-rich repeat domain. Moreover, in vitro studies demonstrated that NLRP12 interacted with TRAF3 and promoted its ubiquitination and degradation, which counteracted the inhibitory effect of TRAF3 on the NF-kappa B/MAPK signaling pathway and promoted the production of inflammatory cytokines. Furthermore, an in vivo study revealed that NLRP12 knockout mice displayed attenuated tissue injury and ameliorated inflammatory responses in the lungs when infected with a SARS-CoV-2 M protein-reconstituted pseudovirus and mouse coronavirus. Taken together, these findings suggest that NLRP12 mediates the inflammatory responses during coronavirus infection.","NLRP12 interacts with the SARS-CoV-2 M protein and promotes the ubiquitination and degradation of TRAF3 to activate the NF-kappa B/MAPK signaling pathways and inflammatory cytokine production."]

inflammation NLRP12 SARS-CoV-2 M protein TRAF3

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China[82072062] ; National Science and Technology Key Projects for Major Infectious Diseases[2017ZX10302301-002] ; Development Project of Foshan Fourth People's Hospital[FSSYKF-2020003] ; Department of Science and Technology of Guangdong Province[2018B030322006] ; Guangdong Medical Science and Technology Research Fund Project[B2022320] ; Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital[202301-102] ; Shenzhen High-level Hospital Construction Fund[G2023001] ; Three Major Scientific Research Projects of Sun Yat-sen University[20200326236] ; Guangdong Scientific and Technological Research Project for COVID-19[2020A111128022] ; Zhuhai Scientific and Technological Research Project for COVID-19[ZH22036302200029PWC] ; Guangdong Science and Technology Special Fund Project[210125176270840]

Immunology ; Infectious Diseases ; Microbiology

Immunology ; Infectious Diseases ; Microbiology

WOS:001104531800001

OXFORD UNIV PRESS INC

IMMUNOLOGY

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China
2.Sun Yat sen Univ, Affiliated Hosp 5, Ctr Infect & Immun, Guangdong Prov Engn Res Ctr Mol Imaging, Zhuhai, Peoples R China
3.Sun Yat sen Univ, Zhongshan Sch Med, Guangzhou, Peoples R China
4.Third Peoples Hosp Shantou, Med Intens Care Unit, Shantou, Peoples R China
5.Yuebei Second Peoples Hosp, TB Prevent & Control Inst, Shaoguan, Peoples R China
6.Guangzhou Med Univ, Qingyuan Peoples Hosp, Affiliated Hosp 6, Qingyuan, Peoples R China
7.Sun Yat sen Univ, Affiliated Hosp 5, Ctr Infect & Immun, Guangdong Prov Engn Res Ctr Mol Imaging, Zhuhai 519000, Guangdong, Peoples R China

Li, Xingyu,Zhou, Guangde,Sun, Xingzi,et al. NLRP12 Senses the SARS-CoV-2 Membrane Protein and Promotes an Inflammatory Response[J]. JOURNAL OF INFECTIOUS DISEASES,2023.

Li, Xingyu.,Zhou, Guangde.,Sun, Xingzi.,Qu, Siying.,Lai, Hongzhi.,...&Huang, Xi.(2023).NLRP12 Senses the SARS-CoV-2 Membrane Protein and Promotes an Inflammatory Response.JOURNAL OF INFECTIOUS DISEASES.

Li, Xingyu,et al."NLRP12 Senses the SARS-CoV-2 Membrane Protein and Promotes an Inflammatory Response".JOURNAL OF INFECTIOUS DISEASES (2023).