title: Interferon-gamma, tumor necrosis factor-alpha, and interleukin 1-beta suppress the replication of hepatitis B virus through oxidative stress.
abstract: The effect of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta), and H2O2, on hepatitis B virus (HBV) replication was analyzed in the HBV DNA transfected human hepatoblastoma-derived cell line HB 611. Secretion of HBV DNA from HB611 cells was inhibited by IFN-gamma, TNF-alpha, IL-1beta, and H2O2 in a dose-dependent manner. These cytokines and H2O2 also decreased HBV mRNA expression in HB611 cells, meaning that these reagents decreased the synthesis of all virally encoded components of the HBV virion. The level of manganese-SOD mRNA, indicative of occurrence of oxidative stress, increased immediately after treatment with IFN-gamma, TNF-alpha, IL-1beta, and H2O2. Moreover, the antioxidant N-acetyl-L-cysteine substantially inhibited the antiviral effect. Our findings suggest that oxidative stress may be a common factor in the antiviral effects of IFN-gamma, TNF-alpha, and IL-1beta on HBV.
authors.affiliation: Second Department of Internal Medicine, Yamagata University School of Medicine, Japan. htogashi@med.id.yamagata-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Togashi
authors.forename: S
authors.initials: S
authors.lastname: Ohno
authors.forename: T
authors.initials: T
authors.lastname: Matsuo
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Shinzawa
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D006515:Hepatitis B virus / Q000187:drug effects*; D018197:Hepatoblastoma / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006861:Hydrogen Peroxide