Molecular characterization of AID-mediated reduction of hepatitis B virus transcripts

Hepatitis B virus (HBV) is the major cause of liver cirrhosis and hepatocellular carcinoma. After entering a hepatocyte, HBV forms a nuclear viral episome and produces pregenomic (pg) RNA with a stem-loop structure called an epsilon, which acts to signal encapsidation. We previously demonstrated that TGF-β upregulates activation-induced cytidine deaminase (AID) expression in hepatocytes, which in turn downregulates HBV transcripts by recruiting the RNA exosome complex. The molecular mechanism underlying AID-mediated HBV RNA reduction remains largely unclear. Here we used a pgRNA reporter system having a reporter gene within pgRNA to identify sis- and trans-acting elements in AID-mediated HBV RNA reduction. We found that the epsilon RNA and C-terminus of AID are required for AID-mediated HBV RNA reduction. Importantly, this reduction was reproduced in a hydrodynamic HBV transfection mouse model. The molecular mechanism of AID-mediated HBV RNA reduction is discussed.