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Updated: Jun 7, 2026

Modeling Hepatitis B Virus Infection in Non-Hepatic 293T-NE-3NRs Cells
Published on: June 5, 2020
Hepatitis B virus induces expression of antioxidant response element-regulated genes by activation of Nrf2
Stephanie Schaedler1, Janis Krause, Kiyoshi Himmelsbach
1Institute of Infection Medicine, Molecular Medical Virology, University of Kiel, D-24105 Kiel, Germany.
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 α/γ 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.
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