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Hepatitis B virus induces expression of antioxidant response element-regulated genes by activation of Nrf2.


ABSTRACT: The expression of a variety of cytoprotective genes is regulated by short cis-acting elements in their promoters, called antioxidant response elements (AREs). A central regulator of ARE-mediated gene expression is the NF-E2-related factor 2 (Nrf2). Human hepatitis B virus (HBV) induces a strong activation of Nrf2/ARE-regulated genes in vitro and in vivo. This is triggered by the HBV-regulatory proteins (HBx and LHBs) via c-Raf and MEK. The Nrf2/ARE-mediated induction of cytoprotective genes by HBV results in a better protection of HBV-positive cells against oxidative damage as compared with control cells. Furthermore, there is a significantly increased expression of the Nrf2/ARE-regulated proteasomal subunit PSMB5 in HBV-positive cells that is associated with a decreased level of the immunoproteasome subunit PSMB5i. In accordance with this finding, HBV-positive cells display a higher constitutive proteasome activity and a decreased activity of the immunoproteasome as compared with control cells even after interferon ?/? treatment. The HBV-dependent induction of Nrf2/ARE-regulated genes might ensure survival of the infected cell, shape the immune response to HBV, and thereby promote establishment of the infection.

SUBMITTER: Schaedler S 

PROVIDER: S-EPMC3003406 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Hepatitis B virus induces expression of antioxidant response element-regulated genes by activation of Nrf2.

Schaedler Stephanie S   Krause Janis J   Himmelsbach Kiyoshi K   Carvajal-Yepes Monica M   Lieder Franziska F   Klingel Karin K   Nassal Michael M   Weiss Thomas S TS   Werner Sabine S   Hildt Eberhard E  

The Journal of biological chemistry 20101018 52


The expression of a variety of cytoprotective genes is regulated by short cis-acting elements in their promoters, called antioxidant response elements (AREs). A central regulator of ARE-mediated gene expression is the NF-E2-related factor 2 (Nrf2). Human hepatitis B virus (HBV) induces a strong activation of Nrf2/ARE-regulated genes in vitro and in vivo. This is triggered by the HBV-regulatory proteins (HBx and LHBs) via c-Raf and MEK. The Nrf2/ARE-mediated induction of cytoprotective genes by H  ...[more]

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