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Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids.
Yang, Qi-Yue; Yang, Yong-Le; Tang, Yi-Xin; Qin, Pan; Wang, Gan; Xie, Jin-Yan; Chen, Shu-Xian; Ding, Chan; Huang, Yao-Wei; Zhu, Shu Jeffrey.
  • Yang QY; Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China.
  • Yang YL; Department of Veterinary Medicine, Zhejiang University, Hangzhou, People's Republic of China.
  • Tang YX; Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China.
  • Qin P; Department of Veterinary Medicine, Zhejiang University, Hangzhou, People's Republic of China.
  • Wang G; Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China.
  • Xie JY; Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China.
  • Chen SX; Key Laboratory of Animal Virology of Ministry of Agriculture, Center for Veterinary Sciences, Zhejiang University, Hangzhou, People's Republic of China.
  • Ding C; Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, People's Republic of China.
  • Huang YW; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People's Republic of China.
  • Zhu SJ; Department of Veterinary Medicine, Zhejiang University, Hangzhou, People's Republic of China.
PLoS Pathog ; 18(6): e1010620, 2022 06.
Article in English | MEDLINE | ID: covidwho-1892334
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Swine Diseases / Coronavirus Infections / Alphacoronavirus Limits: Animals Language: English Journal: PLoS Pathog Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Swine Diseases / Coronavirus Infections / Alphacoronavirus Limits: Animals Language: English Journal: PLoS Pathog Year: 2022 Document Type: Article