Long-term hepatitis B infection in a scalable hepatic co-culture system

Benjamin Y. Winer, Tiffany S. Huang, Eitan Pludwinski, Brigitte Heller, Felix Wojcik, Gabriel E. Lipkowitz, Amit Parekh, Cheul Cho, Anil Shrirao, Tom W. Muir, Eric Novik and Alexander Ploss ()
Additional contact information
Benjamin Y. Winer: Princeton University
Tiffany S. Huang: Princeton University
Eitan Pludwinski: Hurel® Corporation
Brigitte Heller: Princeton University
Felix Wojcik: Princeton University
Gabriel E. Lipkowitz: Princeton University
Amit Parekh: Hurel® Corporation
Cheul Cho: Hurel® Corporation
Anil Shrirao: Hurel® Corporation
Tom W. Muir: Princeton University
Eric Novik: Hurel® Corporation
Alexander Ploss: Princeton University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Hepatitis B virus causes chronic infections in 250 million people worldwide. Chronic hepatitis B virus carriers are at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. A prophylactic vaccine exists and currently available antivirals can suppress but rarely cure chronic infections. The study of hepatitis B virus and development of curative antivirals are hampered by a scarcity of models that mimic infection in a physiologically relevant, cellular context. Here, we show that cell-culture and patient-derived hepatitis B virus can establish persistent infection for over 30 days in a self-assembling, primary hepatocyte co-culture system. Importantly, infection can be established without antiviral immune suppression, and susceptibility is not donor dependent. The platform is scalable to microwell formats, and we provide proof-of-concept for its use in testing entry inhibitors and antiviral compounds.

Date: 2017
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DOI: 10.1038/s41467-017-00200-8

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