2. Academic Validation
  3. Porcine reproductive and respiratory syndrome virus infection inhibits NF-κB signaling pathway through cleavage of IKKβ by Nsp4

Porcine reproductive and respiratory syndrome virus infection inhibits NF-κB signaling pathway through cleavage of IKKβ by Nsp4

  • Vet Microbiol. 2023 Apr 29;282:109767. doi: 10.1016/j.vetmic.2023.109767.
Shuang Jiao 1,  Changyao Li 2,  Hongyang Liu 2,  Mengdi Xue 2,  Qiongqiong Zhou 2,  Longfeng Zhang 2,  Xiaohong Liu 2,  Chunying Feng 2,  Guangqiang Ye 2,  Jia Liu 2,  Jiangnan Li 3,  Li Huang 3,  Tao Xiong 4,  Zhaoxia Zhang 5,  Changjiang Weng 6
Affiliations

Affiliations

  • 1 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China; College of Life Sciences, Yangtze University, Jingzhou 434025, China.
  • 2 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
  • 3 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China; Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin 150069, China.
  • 4 College of Life Sciences, Yangtze University, Jingzhou 434025, China. Electronic address: xiongtao@yangtzeu.edu.cn.
  • 5 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China; Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin 150069, China. Electronic address: zhangzhaoxia@caas.cn.
  • 6 Division of Fundamental Immunology, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China; Heilongjiang Provincial Key Laboratory of Veterinary Immunology, Harbin 150069, China. Electronic address: wengchangjiang@caas.cn.
PMID: 37141805 DOI: 10.1016/j.vetmic.2023.109767
Abstract

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.

Keywords

IKKβ; NF-κB; NSP4; Porcine Reproductive and Respiratory Syndrome virus; Virus replication.

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