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

TitleLong-term hepatitis B infection in a scalable hepatic co-culture system.
Publication TypeJournal Article
Year of Publication2017
AuthorsWiner, BY, Huang, TS, Pludwinski, E, Heller, B, Wojcik, F, Lipkowitz, GE, Parekh, A, Cho, C, Shrirao, A, Muir, TW, Novik, E, Ploss, A
JournalNat Commun
Volume8
Issue1
Pagination125
Date Published2017 Jul 25
ISSN2041-1723
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.The lack of models that mimic hepatitis B virus (HBV) infection in a physiologically relevant context has hampered drug development. Here, Winer et al. establish a self-assembling, primary hepatocyte co-culture system that can be infected with patient-derived HBV without further modifications.

DOI10.1038/s41467-017-00200-8
Alternate JournalNat Commun
PubMed ID28743900
PubMed Central IDPMC5527081
Grant ListR21 AI117213 / AI / NIAID NIH HHS / United States
R37 GM086868 / GM / NIGMS NIH HHS / United States