In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 6 ( 2022-6-13), p. e1010620-
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010620
DOI:
10.1371/journal.ppat.1010620.g001
DOI:
10.1371/journal.ppat.1010620.g002
DOI:
10.1371/journal.ppat.1010620.g003
DOI:
10.1371/journal.ppat.1010620.g004
DOI:
10.1371/journal.ppat.1010620.g005
DOI:
10.1371/journal.ppat.1010620.g006
DOI:
10.1371/journal.ppat.1010620.g007
DOI:
10.1371/journal.ppat.1010620.g008
DOI:
10.1371/journal.ppat.1010620.g009
DOI:
10.1371/journal.ppat.1010620.s001
DOI:
10.1371/journal.ppat.1010620.s002
DOI:
10.1371/journal.ppat.1010620.s003
DOI:
10.1371/journal.ppat.1010620.s004
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2205412-1
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