Title | Long-term hepatitis B infection in a scalable hepatic co-culture system. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Winer, BY, Huang, TS, Pludwinski, E, Heller, B, Wojcik, F, Lipkowitz, GE, Parekh, A, Cho, C, Shrirao, A, Muir, TW, Novik, E, Ploss, A |
Journal | Nat Commun |
Volume | 8 |
Issue | 1 |
Pagination | 125 |
Date Published | 2017 Jul 25 |
ISSN | 2041-1723 |
Keywords | 3T3 Cells, Animals, Antiviral Agents, Carcinoma, Hepatocellular, Cells, Cultured, Coculture Techniques, Fibroblasts, HEK293 Cells, Hep G2 Cells, Hepatitis B virus, Hepatitis B, Chronic, Hepatocytes, Humans, Liver Neoplasms, Mice |
Abstract | <p>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.</p> |
DOI | 10.1038/s41467-017-00200-8 |
Alternate Journal | Nat Commun |
PubMed ID | 28743900 |
PubMed Central ID | PMC5527081 |
Grant List | R21 AI117213 / AI / NIAID NIH HHS / United States R37 GM086868 / GM / NIGMS NIH HHS / United States T32 GM007388 / GM / NIGMS NIH HHS / United States / / Wellcome Trust / United Kingdom |