1. Academic Validation
  2. 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
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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