Roles of bile acids in enteric virus replication

Abstract

Bile acids (BAs) are evolutionally conserved molecules synthesized in the liver from cholesterol to facilitating the absorption of fat-soluble nutrients. In the intestines, where enteric viruses replicate, BAs also act as signaling molecules that modulate various biological functions via activation of specific receptors and cell signaling pathways. To date, BAs present either pro-viral or anti-viral effects for the replication of enteric viruses in vivo and in vitro. In this review, we summarized current information on biosynthesis, transportation and metabolism of BAs and the role of BAs in replication of enteric caliciviruses, rotaviruses, and coronaviruses. We also discussed the application of BAs for cell culture adaptation of fastidious enteric caliciviruses and control of virus infection, which may provide novel insights into the development of antivirals and/or disinfectants for enteric viruses.

Keywords: Bile acids; Calicivirus; Coronavirus; Norovirus; Rotavirus; Sapovirus.

Fig. 1

Bile acid (BA) biosynthesis and metabolism. Schematic representation of synthetic pathways of primary BAs in hepatocytes (tawny color) and secondary BAs in the intestine (dark brown color). The formation of BAs occurs in the liver via 2 pathways: the classical (or neutral) and the alternative (or acidic) pathways. BAs in the liver are then conjugated with glycine (G) or taurine (T). Primary BAs are metabolized by certain gut bacteria by deconjugation, dehydroxylation, conjugation, and epimerization, generating secondary BAs. The majority of BAs in the gut (90-95%) are reabsorbed in the ileum and recirculate to the liver through the portal vein. The remaining BAs are eliminated through the feces. CA, cholic acid. DCA, deoxycholic acid. CDCA, chenodeoxycholic acid. LCA, lithocholic acid. UDCA, ursodeoxycholic acid