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

Research output: Contribution to journalArticle

A. M. Ortega-Prieto, J. K. Skelton, S. N. Wai, E. Large, M. Lussignol, G. Vizcay-Barrena, D. Hughes, R. A. Fleck, M. Thursz, M. T. Catanese, M. Dorner

Original languageEnglish
Article number682
JournalNature Communications
Volume9
Issue number1
Early online date14 Feb 2018
DOIs
Accepted/In press9 Jan 2018
E-pub ahead of print14 Feb 2018
PublishedDec 2018

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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 lines 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.

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