Volume 6 Supplement 1

Epigenetics and Chromatin: Interactions and processes

Open Access

Transcriptome dysregulation and epigenome signature responses in hepatocytes upon hepatitis B virus infection and therapy

  • Andreas Klein1,
  • Lisa Wiluhn1,
  • Theodor Winkler1,
  • Timo Deba1,
  • Valerie Orth1,
  • Kai Hensel1,
  • Andreas Jenke1,
  • Stefan Wirth1 and
  • Jan Postberg1
Epigenetics & Chromatin20136(Suppl 1):P67

https://doi.org/10.1186/1756-8935-6-S1-P67

Published: 18 March 2013

Background

Chronic infection with hepatitis B virus (HBV) induces transregulation of the host cell gene expression and eventually malignant transformation. HBV X protein acts as a transactivator of cellular promoters leading to upregulation of DNA methyltransferases and alterations of DNA methylation patterns.

Aim of the study

To contribute to our understanding of DNA and chromatin-modifying mechanisms modulated by HBV, which are responsible for the transregulation of host cells for virus particle production and malignant transformation of hepatocytes. We further study the effect of lamivudine treatment or an antiviral vector-based RNAi strategy targeting HBx on the establishment and maintenance of DNA methylation patterns. Our research not only aims to uncover epigenomic plasticity modulated by HBV. We also intend to contribute to the open problem, whether therapies lead to the restoration of regular epigenomic signatures, or whether hepatocytes persist in a deregulated epigenetic ‘memory’ state of HBV infection thus still carrying the risk for malignant transformation.

Methods

Therefore we analyze expression profiles by qRT PCR arrays. DNA methylation as well as chromatin signatures of genes up- or downregulated upon HBV infection are studied by MeDIP or ChIP respectively, in murine cell lines infected with HBV.

Results

We identified several transregulated genes and monitored DNA methylation and chromatin signatures at selected loci within promoters. Moreover we observed that therapeutic strategies lead to changes in the epigenomic signature of hepatocytes.

Conclusions

Our data show that our experimental therapeutic interventions efficiently suppress HBV proliferation, whereas an increased risk of malignant transformation cannot be excluded.

Authors’ Affiliations

(1)
Zentrum für Kinder- und Jugendmedizin, HELIOS Klinikum Wuppertal, Universität Witten/Herdecke

Copyright

© Klein et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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