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Abstract

Transmissible gastroenteritis virus (TGEV) is a coronavirus that infects piglets with severe diarrhoea, vomiting, dehydration, and even death, causing huge economic losses to the pig industry. The underlying pathogenesis of TGEV infection and the effects of TGEV infection on host metabolites remain poorly understood. To investigate the critical metabolites and regulatory factors during TGEV infection in intestinal porcine epithelial cells (IPEC-J2), we performed metabolomic and transcriptomic analyses of TGEV-infected IPEC-J2 cells by LC/MS and RNA-seq techniques. A total of 87 differential metabolites and 489 differentially expressed genes were detected. A series of metabolites and candidate genes from glutathione metabolism and AMPK signalling pathway were examined through combined analysis of metabolome and transcriptome. We found glutathione peroxidase 3 () is markedly reduced after TGEV infection, and a significant negative correlation between AMPK signalling pathway and TGEV infection. Exogenous addition of the AMPK activator COH-SR4 significantly downregulates stearoyl coenzyme A () mRNA and inhibits TGEV replication; while exogenous GSK-690693 significantly promotes TGEV infection by inhibiting AMPK signalling pathway. In summary, our study provides insights into the key metabolites and regulators for TGEV infection from the metabolome and transcriptome perspective, which will offer promising antiviral metabolic and molecular targets and enrich the understanding of the existence of a similar mechanism in the host.

Funding
This study was supported by the:
  • Priority Academic Program Development of Jiangsu Higher Education Institutions (Award NA)
    • Principle Award Recipient: WenbinBao
  • Open competition mechanism to select the best candidates Foundation for breeding industry prosperity of Jiangsu Province, China (Award JBGS[2021]098)
    • Principle Award Recipient: WenbinBao
  • Postdoctoral Research Foundation of China (Award 2021M692712)
    • Principle Award Recipient: ShuaiZhang
  • Natural Science Foundation of Jiangsu Province (Award BK20220581)
    • Principle Award Recipient: ShuaiZhang
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/content/journal/jgv/10.1099/jgv.0.001942
2023-12-20
2024-05-21
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