An RNA-based system to study hepatitis B virus replication and select drug-resistance mutations
Yu, Y.; Schneider, W. M.; Michailidis, E.; Acevedo, A.; Ni, Y.; Ambrose, P.; Zou, C.; Kabbani, M.; Quirk, C.; Jahan, C.; Wu, X.; Urban, S.; Shlomai, A.; de Jong, Y. P.; Rice, C. M.
Show abstract
Hepatitis B virus (HBV) chronically infects over 250 million people worldwide, increasing their 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. We describe a method to initiate replication of HBV, a DNA virus, using synthetic RNA. This approach has several advantages over existing systems: it eliminates contaminating background signal from input virus or plasmid DNA and can be easily adapted to multiple genotypes and mutants. Further, it 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.
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