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Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids
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 ac...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249351/ https://www.ncbi.nlm.nih.gov/pubmed/35696443 http://dx.doi.org/10.1371/journal.ppat.1010620 |
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author | 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 |
author_facet | 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 |
author_sort | Yang, Qi-Yue |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9249351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92493512022-07-02 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 PLoS Pathog Research Article 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. Public Library of Science 2022-06-13 /pmc/articles/PMC9249351/ /pubmed/35696443 http://dx.doi.org/10.1371/journal.ppat.1010620 Text en © 2022 Yang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article 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 Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids |
title | Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids |
title_full | Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids |
title_fullStr | Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids |
title_full_unstemmed | Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids |
title_short | Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids |
title_sort | bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249351/ https://www.ncbi.nlm.nih.gov/pubmed/35696443 http://dx.doi.org/10.1371/journal.ppat.1010620 |
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