2. Academic Validation
  3. Lithocholic acid exerts antiviral activity against porcine epidemic diarrhea virus by enhancing TGR5-mediated type III interferon production

Lithocholic acid exerts antiviral activity against porcine epidemic diarrhea virus by enhancing TGR5-mediated type III interferon production

  • Microb Pathog. 2026 Jan:210:108187. doi: 10.1016/j.micpath.2025.108187.
Haiyan He 1,  Haiyan Shen 2,  Chunhong Zhang 2,  Kunli Zhang 2,  Yunzhi Qu 2,  Jingjing Nie 2,  Aiqing Jia 3,  Jianfeng Zhang 4,  Zhicheng Liu 5
Affiliations

Affiliations

  • 1 College of Animal Science and Technology, Ningxia University, Yinchuan, 750021, PR China; Guangdong Province Key Laboratory of Livestock Disease Prevention, State Key Laboratory of Swine and Poultry Breeding Industry, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, PR China; College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010010, PR China.
  • 2 Guangdong Province Key Laboratory of Livestock Disease Prevention, State Key Laboratory of Swine and Poultry Breeding Industry, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, PR China.
  • 3 Guangdong Provincial Key Laboratory of Research on the Technology of Pig-breeding and Pig-disease Prevention, Guangdong Haid Animal Husbandry and Veterinary Research Institute, Guangzhou, 511400, PR China.
  • 4 Guangdong Province Key Laboratory of Livestock Disease Prevention, State Key Laboratory of Swine and Poultry Breeding Industry, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, PR China. Electronic address: [email protected].
  • 5 Guangdong Province Key Laboratory of Livestock Disease Prevention, State Key Laboratory of Swine and Poultry Breeding Industry, Institute of Animal Health, Guangdong Academy of Agricultural Sciences, Guangzhou, 510640, PR China. Electronic address: [email protected].
PMID: 41242567 DOI: 10.1016/j.micpath.2025.108187
Abstract

Background: Porcine epidemic diarrhea virus (PEDV), a highly infectious porcine virus, leads to high mortality in newborn piglets. Bile acids (BAs) are synthesized in the liver and metabolized in the intestines by gut microbiota. These acids can regulate cellular immunity and influence viral Infection processes.

Aim: To assess the Antiviral activity of four BAs-cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and lithocholic acid (LCA) against PEDV in IPEC-J2 cells.

Methodology: We investigated the effects of 24-h pretreatment with the four aforementioned BAs at varying concentrations on PEDV replication in IPEC-J2 cells through quantitative polymerase chain reaction (qPCR), Western blotting, and TCID50 assay.

Results: BA exposure inhibited PEDV N protein expression to varying degrees. qPCR and Western blotting to measure PEDV N protein and mRNA expression at varying LCA concentrations (1, 5, or 10 μM) revealed that LCA demonstrated significant anti-PEDV activity in a concentration-dependent manner (p < 0.05). Time-of-addition assay confirmed that LCA predominantly inhibits PEDV Infection at the replication stage. Thus, LCA activates transcription of the type III interferon (IFN) gene, 2'-5'-oligoadenylate synthetase 1 gene, and IFN-stimulated gene 15 (ISG15). Moreover, 24-h pretreatment with 100 nM SBI-115 (receptor inhibitor) and LCA blocked Takeda G protein-coupled receptor 5 in IPEC-J2 cells, effectively inhibiting type III interferon and ISG15 expression and promoting PEDV proliferation.

Conclusion: LCA primarily targets Takeda G protein-coupled receptor 5 by inducing type III interferon, inhibiting PEDV proliferation. Therefore, LCA may be included in therapeutic strategies targeting PEDV. These results collectively highlight the potential of LCA as a therapeutic agent against PEDV by targeting the viral replication process, providing a novel strategy to control PEDV infections.

Keywords

IFN-λ; Lithocholic acid; PEDV; Takeda G protein-coupled receptor 5.

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