An RNA-based system to initiate hepatitis B virus infection

Hepatitis B virus (HBV) chronically infects over 250 million people worldwide, putting them at risk of liver cirrhosis and hepatocellular carcinoma. There is a vaccine to prevent new infections, but no efficient cure for chronic infection. New insights into HBV biology are needed to improve cure rates for this widespread devastating disease. Here we describe a method to launch HBV infection with RNA, which has advantages over existing systems: it eliminates contaminating background signal from input virus or plasmid DNA and can be easily adapted to study multiple genotypes and mutants. The method can be applied to identify anti-HBV compounds, measure anti-HBV drug efficiency, study virus evolution, and, as we demonstrate, it can be uniquely applied to predict antiviral drug resistance.