Rotaviruses (group A rotaviruses) are the most important cause of severe
gastroenteritis in infants and children worldwide. Currently, an
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 the following. First, the intracellular contents of
triglycerides were significantly increased by
rotavirus infection. Second, CDCA,
deoxycholic acid (DCA), and other synthetic FXR agonists, such as
GW4064, significantly reduced rotavirus replication in cell culture in a dose-dependent manner. The reduction of virus replication correlated positively with activation of the FXR pathway and reduction of cellular
triglyceride contents (r(2) = 0.95). Third,
oral administration of CDCA significantly reduced fecal virus shedding in mice (P < 0.05). We conclude that
bile acids and FXR agonists play important roles in the suppression of rotavirus replication. The inhibition mechanism is proposed to be the downregulation of
lipid synthesis induced by
rotavirus infection.