1. Academic Validation
  2. Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids

Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids

  • PLoS Pathog. 2022 Jun 13;18(6):e1010620. doi: 10.1371/journal.ppat.1010620.
Qi-Yue Yang 1 Yong-Le Yang 2 Yi-Xin Tang 1 Pan Qin 2 Gan Wang 1 Jin-Yan Xie 1 Shu-Xian Chen 1 Chan Ding 3 4 Yao-Wei Huang 2 5 Shu Jeffrey Zhu 1 6
Affiliations

Affiliations

  • 1 Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China.
  • 2 Department of Veterinary Medicine, Zhejiang University, Hangzhou, People's Republic of China.
  • 3 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, People's Republic of China.
  • 4 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People's Republic of China.
  • 5 Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, People's Republic of China.
  • 6 Department of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
Abstract

Intestinal microbial metabolites have been increasingly recognized as important regulators of enteric viral Infection. However, very little information is available about which specific microbiota-derived metabolites are crucial for swine enteric coronavirus (SECoV) Infection in vivo. Using swine acute diarrhea syndrome (SADS)-CoV as a model, we were able to identify a greatly altered bile acid (BA) profile in the small intestine of infected piglets by untargeted metabolomic analysis. Using a newly established ex vivo model-the stem cell-derived porcine intestinal enteroid (PIE) culture-we demonstrated that certain BAs, cholic acid (CA) in particular, enhance SADS-CoV replication by acting on PIEs at the early phase of Infection. We ruled out the possibility that CA exerts an augmenting effect on viral replication through classic farnesoid X receptor or Takeda G protein-coupled receptor 5 signaling, innate immune suppression or viral attachment. BA induced multiple cellular responses including rapid changes in caveolae-mediated endocytosis, endosomal acidification and dynamics of the endosomal/lysosomal system that are critical for SADS-CoV replication. Thus, our findings shed LIGHT on how SECoVs exploit microbiome-derived metabolite BAs to swiftly establish viral Infection and accelerate replication within the intestinal microenvironment.

Figures
Products