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

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 infection...

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Autores principales: Winer, Benjamin Y., Huang, Tiffany S., Pludwinski, Eitan, Heller, Brigitte, Wojcik, Felix, Lipkowitz, Gabriel E., Parekh, Amit, Cho, Cheul, Shrirao, Anil, Muir, Tom W., Novik, Eric, Ploss, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527081/
https://www.ncbi.nlm.nih.gov/pubmed/28743900
http://dx.doi.org/10.1038/s41467-017-00200-8
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author Winer, Benjamin Y.
Huang, Tiffany S.
Pludwinski, Eitan
Heller, Brigitte
Wojcik, Felix
Lipkowitz, Gabriel E.
Parekh, Amit
Cho, Cheul
Shrirao, Anil
Muir, Tom W.
Novik, Eric
Ploss, Alexander
author_facet Winer, Benjamin Y.
Huang, Tiffany S.
Pludwinski, Eitan
Heller, Brigitte
Wojcik, Felix
Lipkowitz, Gabriel E.
Parekh, Amit
Cho, Cheul
Shrirao, Anil
Muir, Tom W.
Novik, Eric
Ploss, Alexander
author_sort Winer, Benjamin Y.
collection PubMed
description 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.
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spelling pubmed-55270812017-07-31 Long-term hepatitis B infection in a scalable hepatic co-culture system Winer, Benjamin Y. Huang, Tiffany S. Pludwinski, Eitan Heller, Brigitte Wojcik, Felix Lipkowitz, Gabriel E. Parekh, Amit Cho, Cheul Shrirao, Anil Muir, Tom W. Novik, Eric Ploss, Alexander Nat Commun Article 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. Nature Publishing Group UK 2017-07-25 /pmc/articles/PMC5527081/ /pubmed/28743900 http://dx.doi.org/10.1038/s41467-017-00200-8 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Winer, Benjamin Y.
Huang, Tiffany S.
Pludwinski, Eitan
Heller, Brigitte
Wojcik, Felix
Lipkowitz, Gabriel E.
Parekh, Amit
Cho, Cheul
Shrirao, Anil
Muir, Tom W.
Novik, Eric
Ploss, Alexander
Long-term hepatitis B infection in a scalable hepatic co-culture system
title Long-term hepatitis B infection in a scalable hepatic co-culture system
title_full Long-term hepatitis B infection in a scalable hepatic co-culture system
title_fullStr Long-term hepatitis B infection in a scalable hepatic co-culture system
title_full_unstemmed Long-term hepatitis B infection in a scalable hepatic co-culture system
title_short Long-term hepatitis B infection in a scalable hepatic co-culture system
title_sort long-term hepatitis b infection in a scalable hepatic co-culture system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527081/
https://www.ncbi.nlm.nih.gov/pubmed/28743900
http://dx.doi.org/10.1038/s41467-017-00200-8
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