3D microfluidic liver cultures as physiological preclinical tool for hepatitis B virus infection

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Title: 3D microfluidic liver cultures as physiological preclinical tool for hepatitis B virus infection
Author(s): Ortega-Prieto, AM
Skelton, JK
Wai, SN
Large, E
Lussignol, M
Vizcay-Barrena, G
Hughes, D
Fleck, R
Thursz, M
Catanese, MT
Dorner, M
Item Type: Journal Article
Abstract: With more than 240 million people infected, hepatitis B virus (HBV) is a major health concern. The inability to mimic the complexity of the liver using cell line and regular primary human hepatocyte (PHH) cultures pose significant limitations for studying host/pathogen interactions. Here, we describe a 3D-microfluidic PHH system permissive to HBV infection, which can be maintained for at least 40 days. This system enables the recapitulation of all steps of the HBV life cycle, including the replication of patient-derived HBV and the maintenance of HBV cccDNA. We show that innate immune and cytokine responses following infection with HBV mimic those observed in HBV-infected patients, thus allowing the dissection of pathways important for immune evasion and validation of biomarkers. Additionally, we demonstrate that the co-culture of PHH with other non-parenchymal cells enables the identification of the cellular origin of immune effectors, thus providing a valuable preclinical platform for HBV research.
Editor(s): Legate, K
Publication Date: 14-Feb-2018
Date of Acceptance: 3-Jan-2018
URI: http://hdl.handle.net/10044/1/55649
DOI: https://dx.doi.org/10.1038/s41467-018-02969-8
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 9
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
CN Bio Innovations Limited
Wellcome Trust
European Research Council
Commission of the European Communities
Funder's Grant Number: RDA15 79560
N/A
104771/Z/14/Z
637304
Copyright Statement: © The Author(s) 2018. 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/
Keywords: MD Multidisciplinary
Publication Status: Published
Article Number: ARTN 682
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



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