Farnesoid X receptor-α is a proviral host factor for hepatitis B virus that is inhibited by ligands in vitro and in vivo

What is it about?

Hepatitis B is still a major public health problem with more than 250 million people chronically infected by hepatitis B virus (HBV) worldwide. Whilst this number seems impressive, it is a small fraction of the two billion individuals that have been infected by HBV. Infections early in life generally induce chronic hepatitis B while infections in adult are often self-limiting. Host factors that influence infection evolution and lead to stable establishment and expression of the viral genome (cccDNA) in hepatocytes remain largely unknown. Interestingly, clinical and in vitro observations suggest reciprocal interactions between bile acids (BA) metabolism and HBV. HBV and BA compete for hepatic BA transporter with consequences on BA cellular concentration and activation of the BA nuclear receptor FXR functions and expression. FXR binds the HBV regulatory region and treatments with FXR agonists repress HBV replication in two cell models of HBV infection. Here we show that FXR favours cccDNA pool formation and transcription by two mechanisms inhibited by FXR agonist. In a mouse model of HBV infection, treatment with an FXR agonist decreased HBV replication in adult but not in young mice. These data further support a role for FXR in the control of hepatitis B evolution.

Featured Image