Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783252913760501760 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5527081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT winerbenjaminy longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT huangtiffanys longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT pludwinskieitan longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT hellerbrigitte longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT wojcikfelix longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT lipkowitzgabriele longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT parekhamit longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT chocheul longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT shriraoanil longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT muirtomw longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT novikeric longtermhepatitisbinfectioninascalablehepaticcoculturesystem AT plossalexander longtermhepatitisbinfectioninascalablehepaticcoculturesystem |