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, Thomas William Muir, Eric Novik, Alexander Ploss

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish (US)
Article number125
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Winer, B. Y., Huang, T. S., Pludwinski, E., Heller, B., Wojcik, F., Lipkowitz, G. E., Parekh, A., Cho, C., Shrirao, A., Muir, T. W., Novik, E., & Ploss, A. (2017). Long-term hepatitis B infection in a scalable hepatic co-culture system. Nature communications, 8(1), [125]. https://doi.org/10.1038/s41467-017-00200-8