Arsenic trioxide inhibits hepatitis C Virus RNA replication through modulation of the glutathione redox system and oxidative stress

Misao Kuroki, Yasuo Ariumi, Masanori Ikeda, Hiromichi Dansako, Takaji Wakita, Nobuyuki Kato

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Arsenic trioxide (ATO), a therapeutic reagent used for the treatment of acute promyelocytic leukemia, has recently been reported to increase human immunodeficiency virus type 1 infectivity. However, in this study, we have demonstrated that replication of genome-length hepatitis C virus (HCV) RNA (O strain of genotype 1b) was notably inhibited by ATO at submicromolar concentrations without cell toxicity. RNA replication of HCV-JFH1 (genotype 2a) and the release of core protein into the culture supernatants were also inhibited by ATO after the HCV infection. To clarify the mechanism of the anti-HCV activity of ATO, we examined whether or not PML is associated with this anti-HCV activity, since PML is known to be a target of ATO. Interestingly, we observed the cytoplasmic translocation of PML after treatment with ATO. However, ATO still inhibited the HCV RNA replication even in the PML knockdown cells, suggesting that PML is dispensable for the anti-HCV activity of ATO. In contrast, we found that VV-acetyl-cysteine, an antioxidant and glutathione precursor, completely and partially eliminated the anti-HCV activity of ATO after 24 h and 72 h of treatment, respectively. In this context, it is worth noting that we found an elevation of intracellular superoxide anion radical, but not hydrogen peroxide, and the depletion of intracellular glutathione in the ATO-treated cells. Taken together, these findings suggest that ATO inhibits the HCV RNA replication through modulation of the glutathione redox system and oxidative stress.

Original languageEnglish
Pages (from-to)2338-2348
Number of pages11
JournalJournal of Virology
Volume83
Issue number5
DOIs
Publication statusPublished - Mar 1 2009

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Arsenic trioxide inhibits hepatitis C Virus RNA replication through modulation of the glutathione redox system and oxidative stress'. Together they form a unique fingerprint.

  • Cite this