An RNA-based system to study hepatitis B virus replication and evaluate antivirals

  • Sci Adv. 2023 Apr 14;9(15):eadg6265. doi: 10.1126/sciadv.adg6265.
Yingpu Yu  1 ,  William M Schneider  1 ,  Maximilian A Kass  1  2 ,  Eleftherios Michailidis  1 ,  Ashley Acevedo  1 ,  Ana L Pamplona Mosimann  1 ,  Juliano Bordignon  1 ,  Alexander Koenig  3 ,  Christine M Livingston  3 ,  Hardeep van Gijzel  4 ,  Yi Ni  5 ,  Pradeep M Ambrose  1  6 ,  Catherine A Freije  1 ,  Mengyin Zhang  1 ,  Chenhui Zou  1  7 ,  Mohammad Kabbani  1  8 ,  Corrine Quirk  1 ,  Cyprien Jahan  1 ,  Xianfang Wu  1 ,  Stephan Urban  2  5 ,  Shihyun You  3 ,  Amir Shlomai  1 ,  Ype P de Jong  1  7 ,  Charles M Rice  1
Affiliations
  • 1. Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • 2. Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany.
  • 3. Infectious Diseases Research Unit, GSK, Upper Providence, PA 19426, USA.
  • 4. Computational Biology, Genome Sciences, GSK, Stevenage, UK.
  • 5. German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany.
  • 6. Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY 10065, USA.
  • 7. Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY 10065, USA.
  • 8. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
PMID: 37043562 DOI: 10.1126/sciadv.adg6265
Abstract

Hepatitis B virus (HBV) chronically infects an estimated 300 million people, and standard treatments are rarely curative. Infection increases the risk of liver cirrhosis and hepatocellular carcinoma, and consequently, nearly 1 million people die each year from chronic hepatitis B. Tools and approaches that bring insights into HBV biology and facilitate the discovery and evaluation of Antiviral drugs are in demand. Here, we describe a method to initiate the replication of HBV, a DNA virus, using synthetic RNA. This approach eliminates contaminating background signals from input virus or plasmid DNA that plagues existing systems and can be used to study multiple stages of HBV replication. We further demonstrate that this method can be uniquely applied to identify sequence variants that confer resistance to Antiviral drugs.

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