1. Hydrogen Peroxide Inhibits Hepatitis B Virus Replication by Downregulating HBx Levels via Siah-1-Mediated Proteasomal Degradation in Human Hepatoma Cells.
- Author
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Yoon H, Lee HK, and Jang KL
- Subjects
- Humans, Hydrogen Peroxide pharmacology, Tumor Suppressor Protein p53 genetics, Virus Replication, Viral Regulatory and Accessory Proteins drug effects, Trans-Activators drug effects, Carcinoma, Hepatocellular genetics, Hepatitis B, Hepatitis B virus drug effects, Liver Neoplasms genetics
- Abstract
The hepatitis B virus (HBV) is constantly exposed to significant oxidative stress characterized by elevated levels of reactive oxygen species (ROS), such as H
2 O2 , during infection in hepatocytes of patients. In this study, we demonstrated that H2 O2 inhibits HBV replication in a p53-dependent fashion in human hepatoma cell lines expressing sodium taurocholate cotransporting polypeptide. Interestingly, H2 O2 failed to inhibit the replication of an HBV X protein (HBx)-null HBV mutant, but this defect was successfully complemented by ectopic expression of HBx. Additionally, H2 O2 upregulated p53 levels, leading to increased expression of seven in absentia homolog 1 (Siah-1) levels. Siah-1, an E3 ligase, induced the ubiquitination-dependent proteasomal degradation of HBx. The inhibitory effect of H2 O2 was nearly abolished not only by treatment with a representative antioxidant, N-acetyl-L-cysteine but also by knockdown of either p53 or Siah-1 using specific short hairpin RNA, confirming the role of p53 and Siah-1 in the inhibition of HBV replication by H2 O2 . The present study provides insights into the mechanism that regulates HBV replication under conditions of oxidative stress in patients.- Published
- 2023
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