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Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models

Liu, Peter Jianrui and Harris, James M and Marchi, Emanuele and D’Arienzo, Valentina and Michler, Thomas and Wing, Peter AC and Magri, Andrea and Ortega-Prieto, Anna Maria and van de Klundert, Maarten and Wettengel, Jochen and Durantel, David and Dorner, Marcus and Klenerman, Paul and Protzer, Ulrike and Giotis, Efstathios S and McKeating, Jane A (2020) 'Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models.' Scientific Reports, 10 (1). 14101-. ISSN 2045-2322

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Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. The prolyl hydroxylase domain (PHD)-hypoxia inducible factor (HIF) pathway is a key mammalian oxygen sensing pathway and is frequently perturbed by pathological states including infection and inflammation. We discovered a significant upregulation of hypoxia regulated gene transcripts in patients with chronic hepatitis B (CHB) in the absence of liver cirrhosis. We used state-of-the-art in vitro and in vivo HBV infection models to evaluate a role for HBV infection and the viral regulatory protein HBx to drive HIF-signalling. HBx had no significant impact on HIF expression or associated transcriptional activity under normoxic or hypoxic conditions. Furthermore, we found no evidence of hypoxia gene expression in HBV de novo infection, HBV infected human liver chimeric mice or transgenic mice with integrated HBV genome. Collectively, our data show clear evidence of hypoxia gene induction in CHB that is not recapitulated in existing models for acute HBV infection, suggesting a role for inflammatory mediators in promoting hypoxia gene expression.

Item Type: Article
Uncontrolled Keywords: Liver; Cell Line, Tumor; Animals; Mice, Inbred C57BL; Mice, Transgenic; Humans; Mice; Hepatitis B, Chronic; Liver Cirrhosis; Disease Models, Animal; Oxygen; Trans-Activators; Cell Hypoxia; Oxidative Stress; Female; Male; Basic Helix-Loop-Helix Transcription Factors; Hypoxia-Inducible Factor 1, alpha Subunit; Viral Regulatory and Accessory Proteins; Hep G2 Cells; Hypoxia-Inducible Factor-Proline Dioxygenases
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 08 Oct 2020 16:24
Last Modified: 18 Aug 2022 10:39

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