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

TY - JOUR

T1 - 3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection

AU - Ortega-Prieto, A. M.

AU - Skelton, J. K.

AU - Wai, S. N.

AU - Large, E.

AU - Lussignol, M.

AU - Vizcay-Barrena, G.

AU - Hughes, D.

AU - Fleck, R. A.

AU - Thursz, M.

AU - Catanese, M. T.

AU - Dorner, M.

PY - 2018/12/31

Y1 - 2018/12/31

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85042083931

U2 - 10.1038/s41467-018-02969-8

DO - 10.1038/s41467-018-02969-8

M3 - Article

C2 - 29445209

AN - SCOPUS:85042083931

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 682

ER -