| Inhibitory Effects of Bile Acids and Synthetic Farnesoid X Receptor Agonists on Rotavirus Replication. | |
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MedLine Citation:
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PMID: 21957312 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Rotaviruses (group A rotaviruses) are the most important cause of severe gastroenteritis in infants and children worldwide. Currently, antiviral drug is not available and information on therapeutic targets for antiviral development is limited for rotavirus infection. Previously, it was shown that lipid homeostasis is important in rotavirus replication. Since farnesoid X receptor (FXR) and its natural ligands, bile acids (such as chenodeoxycholic acid, CDCA), play major roles in cholesterol and lipid homeostasis, we examined the effects of bile acids and synthetic FXR agonists on rotavirus replication in association with cellular lipid levels. In a mouse model of rotavirus infection, effects of oral administration of CDCA on fecal rotavirus shedding were investigated. The results demonstrate that, first, the intracellular contents of tryglycerides were significantly increased by rotavirus infection. Second, CDCA, deoxycholic acid (DCA) and other synthetic FXR agonists such as GW4064 significantly reduced rotavirus replication in a dose-dependent manner in cell culture. The reduction of virus replication correlated positively with the activation of FXR pathway and reduction of cellular triglycerides contents (r(2) = .95). Third, oral administration of CDCA significantly reduced the fecal virus shedding in mice (P < .05). We conclude that bile acids and FXR agonists play important roles in the suppression of rotavirus replication. The inhibition mechanism is proposed as the down-regulation of lipids synthesis induced by rotavirus infection. |
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Authors:
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Yunjeong Kim; Kyeong-Ok Chang |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-28 |
Journal Detail:
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Title: Journal of virology Volume: - ISSN: 1098-5514 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-29 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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