Nov 27, 2014

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

BioRxiv : the Preprint Server for Biology
Marcus M DillonJane A McKeating

Abstract

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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Mentioned in this Paper

Genome-Wide Association Study
Size
Genome
Malignant Neoplasm of Stomach
Pathogenic Organism
Gene Deletion Abnormality
Gene Deletion
Deletion Mutation
Nucleotides
Chromosomes

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