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.

doi:10.1101/787630

bioRxiv · 10.1101/787630

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.

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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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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.. 2019-10-02. An RNA-based system to study hepatitis B virus replication and select drug-resistance mutations. https://doi.org/10.1101/787630

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