猪繁殖与呼吸综合征病毒
IκB激酶
生物
先天免疫系统
丝氨酸
NF-κB
信号转导
蛋白质亚单位
磷酸化
转录因子
细胞生物学
NFKB1型
病毒学
激酶
丝氨酸蛋白酶
免疫系统
分子生物学
病毒
基因
蛋白酶
遗传学
生物化学
酶
作者
Shuliang Jiao,Changyao Li,Hongyang Li,Mei Xue,Qi Zhou,Longfeng Zhang,Xiaohong Liu,Chunying Feng,Guangqiang Ye,Jia Liu,Jiangnan Li,Huang Li,Tao Xiong,Zhaoxia Zhang,Changjiang Weng
标识
DOI:10.1016/j.vetmic.2023.109767
摘要
Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious porcine pathogen that causes serious economic losses to the world swine industry. The inhibitor kappa B kinase β (IKKβ), a catalytic subunit of the IKK complex, plays multiple roles in regulating the nuclear transcription factor kappa B (NF-κB) activity and a variety of cytokines transcription involved in immune responses. Here, we reported that the nonstructural protein 4 (Nsp4) of PRRSV cleaved IKKβ at the E378 site to inhibit the activation of NF-κB signaling pathway. Additionally, we clearly showed that cleavage of IKKβ by PRRSV Nsp4 depends on the 3 C-like serine protease activity of Nsp4 because the catalytically inactivate mutants of Nsp4 lost the function to cleave IKKβ. Furthermore, we found that hydrophobic patch at the KD-ULD junction of IKKβ could be disrupted by PRRSV Nsp4 via the cleavage of the E378 site, resulting in disruption of NF-κB activity. Of note, the two cleavage fragments of IKKβ lose their function to phosphorylate IκBα and activate NF-κB signaling pathway. Our findings provide a clue to better understand the pathogenic mechanism of PRRSV involved in PRRSV evasion of host antiviral innate immune responses.
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