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Inhibitory effects of bile acids and synthetic farnesoid X receptor agonists on rotavirus replication

Yunjeong Kim1, Kyeong-Ok Chang

  • 1Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA. ykim@vet.ksu.edu

Journal of Virology
|September 30, 2011
PubMed

Insights

Bile acids and farnesoid X receptor (FXR) agonists reduce rotavirus replication by regulating lipid synthesis. This study shows potential therapeutic targets for developing new antiviral drugs against rotavirus infection.

Area of Science:

  • Virology
  • Biochemistry
  • Pharmacology

Background:

  • Rotaviruses cause severe gastroenteritis in children globally.
  • No specific antiviral drugs are currently available for rotavirus infection.
  • Lipid homeostasis is crucial for rotavirus replication.

Purpose of the Study:

  • To investigate the effect of bile acids and farnesoid X receptor (FXR) agonists on rotavirus replication.
  • To explore the association between cellular lipid levels and rotavirus replication.
  • To evaluate the therapeutic potential of FXR agonists against rotavirus infection.

Main Methods:

  • Cell culture experiments to assess rotavirus replication.
  • Treatment with bile acids (CDCA, DCA) and synthetic FXR agonists (GW4064).
  • Measurement of intracellular triglyceride levels.
  • In vivo study using a mouse model of rotavirus infection.

Main Results:

  • Rotavirus infection significantly increased intracellular triglyceride levels.
  • CDCA, DCA, and GW4064 dose-dependently reduced rotavirus replication in cell culture.
  • Reduced viral replication correlated with FXR pathway activation and decreased triglyceride levels (r(2) = 0.95).
  • Oral CDCA administration significantly reduced fecal rotavirus shedding in mice.

Conclusions:

  • Bile acids and FXR agonists effectively suppress rotavirus replication.
  • The mechanism involves downregulating lipid synthesis pathways disrupted by rotavirus infection.
  • FXR agonists represent promising therapeutic targets for rotavirus antiviral development.

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