2. Academic Validation
  3. Nonstructural protein 14 of PDCoV promotes complement C3 expression via the activation of p38-MAPK-C/EBP pathway

Nonstructural protein 14 of PDCoV promotes complement C3 expression via the activation of p38-MAPK-C/EBP pathway

  • Vet Microbiol. 2024 Jun 3:295:110137. doi: 10.1016/j.vetmic.2024.110137.
Zhuoqi Chen 1,  Chunyan Zhong 2,  Liyuan Fan 1,  Hongqi Shang 1,  Li Xiao 3,  Wei Wang 1,  Rongli Guo 1,  Baochao Fan 4,  Jizong Li 5,  Bin Li 6
Affiliations

Affiliations

  • 1 Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Nanjing 210014, China; Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing 210014, China.
  • 2 Biological Engineering Department, Southwest Guizhou Vocational and Technical College for Nationalities, Xingyi 562400, China.
  • 3 Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Nanjing 210014, China.
  • 4 Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Nanjing 210014, China; Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing 210014, China; Institute of Life Sciences, School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou 225009, China; Guotai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou 225300, China.
  • 5 Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Nanjing 210014, China; Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing 210014, China; Institute of Life Sciences, School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou 225009, China; Guotai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou 225300, China. Electronic address: lijizong22@sina.com.
  • 6 Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Nanjing 210014, China; Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing 210014, China; Institute of Life Sciences, School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China; College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou 225009, China; Guotai (Taizhou) Center of Technology Innovation for Veterinary Biologicals, Taizhou 225300, China. Electronic address: libinana@126.com.
PMID: 38851153 DOI: 10.1016/j.vetmic.2024.110137
Abstract

Porcine deltacoronavirus (PDCoV) is an emergent enteric coronavirus, primarily inducing diarrhea in swine, particularly in nursing piglets, with the additional potential for zoonotic transmission to humans. Despite the significant impact of PDCoV on swine populations, its pathogenic mechanisms remain incompletely understood. Complement Component 3 (C3) plays a pivotal role in the prevention of viral infections, however, there are no reports concerning the influence of C3 on the proliferation of PDCoV. In this study, we initially demonstrated that PDCoV is capable of activating the C3 and eliciting inflammatory responses. The overexpression of C3 significantly suppressed PDCoV replication, while inhibition of C3 expression facilitated PDCoV replication. We discovered that nonstructural proteins Nsp7, Nsp14, and M, considerably stimulated C3 expression, particularly Nsp14, through activation of the p38-MAPK-C/EBP-β pathway. The N7-MTase constitutes a significant functional domain of the non-structural protein Nsp14, which is more obvious to upregulate C3. Furthermore, functional mutants of the N7-MTase domain suggested that the D44 and T135 of N7-Mtase constituted a pivotal amino acid site to promote C3 expression. This provides fresh insights into comprehending how the virus manipulates the host immune response and suggests potential Antiviral strategies against PDCoV.

Keywords

C/EBP-β; C3; Complement; Nsp14; PDCoV.

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