SARS-CoV-2 ORF3a positively regulates NF-?B activity by enhancing IKK?-NEMO interaction

被引:11
作者
Nie, Ying [1 ]
Mou, Lumin [1 ,2 ]
Long, Qizhou [1 ]
Deng, Dongqing [1 ]
Hu, Rongying [3 ]
Cheng, Jinzhi [1 ]
Wu, Jiahong [1 ,2 ]
机构
[1] Guizhou Med Univ, Coll Basic Med Sci, Dept Parasitol, Prov Key Lab Modern Pathogen Biol, Guiyang 550025, Peoples R China
[2] Guizhou Med Univ, Sch Publ Hlth, Key Lab Environm Pollut Monitoring & Dis Control, Minist Educ, Guiyang 550025, Peoples R China
[3] Guizhou Med Univ, Affiliated Hosp, Guiyang 550004, Peoples R China
基金
中国国家自然科学基金;
关键词
SARS-CoV-2; ORF3a; Inflammation; NF-?B; IKK; NEMO; KAPPA-B; NLRP3; INFLAMMASOME; INHIBITION; APOPTOSIS; CANCER; IMMUNITY; PROTEIN; BETA; LINE;
D O I
10.1016/j.virusres.2023.199086
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection. Patients with severe COVID-19 exhibit robust induction of proinflammatory cytokines, which are closely associated with the devel-opment of acute respiratory distress syndrome. However, the underlying mechanisms of the NF-kappa B activation mediated by SARS-CoV-2 infection remain poorly understood. Here, we screened SARS-CoV-2 genes and found that ORF3a induces proinflammatory cytokines by activating the NF-kappa B pathway. Moreover, we found that ORF3a interacts with IKK beta and NEMO and enhances the interaction of IKK beta-NEMO, thereby positively regulating NF-kappa B activity. Together, these results suggest ORF3a may play pivotal roles in the pathogenesis of SARS-CoV-2 and provide novel insights into the interaction between host immune responses and SARS-CoV-2 infection.
引用
收藏
页数:9
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