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

Author:

Yu Yingpu1ORCID,Schneider William M.1ORCID,Kass Maximilian A.12ORCID,Michailidis Eleftherios1ORCID,Acevedo Ashley1ORCID,Pamplona Mosimann Ana L.1ORCID,Bordignon Juliano1ORCID,Koenig Alexander3,Livingston Christine M.3,van Gijzel Hardeep4,Ni Yi5ORCID,Ambrose Pradeep M.16,Freije Catherine A.1ORCID,Zhang Mengyin1ORCID,Zou Chenhui17,Kabbani Mohammad18ORCID,Quirk Corrine1ORCID,Jahan Cyprien1,Wu Xianfang1ORCID,Urban Stephan25,You Shihyun3ORCID,Shlomai Amir1ORCID,de Jong Ype P.17,Rice Charles M.1ORCID

Affiliation:

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.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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