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Liu, P.J.* ; Harris, J.M.* ; Marchi, E.* ; D’Arienzo, V.* ; Michler, T. ; Wing, P.A.C.* ; Magri, A.* ; Ortega-Prieto, A.M.* ; van de Klundert, M. ; Wettengel, J.M. ; Durantel, D.* ; Dorner, M.* ; Klenerman, P.* ; Protzer, U. ; Giotis, E.S.* ; McKeating, J.A.*

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

Sci. Rep. 10:14101 (2020)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter X-protein; Inducible Factor-1-alpha; Activation; Liver; Inflammation; Alpha; Replication; Mechanisms; Pathways; Genome
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Zeitschrift Scientific Reports
Quellenangaben Band: 10, Heft: 1, Seiten: , Artikelnummer: 14101 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Förderungen ERC
EU Horizon 2020 program through the Hep-CAR consortium
Institute for Advanced Study
Technische Universitat Munchen via the German Excellence Initiative
Wellcome grant
Wellcome Trust