S-adenosylmethionine and betaine correct hepatitis C virus induced inhibition of interferon signaling in vitro

Authors

  • Francois H. T. Duong,

    1. Department of Research and Division of Gastroenterology and Hepatology, University Hospital Basel, Switzerland
    Search for more papers by this author
  • Verena Christen,

    1. Department of Research and Division of Gastroenterology and Hepatology, University Hospital Basel, Switzerland
    Search for more papers by this author
  • Magdalena Filipowicz,

    1. Department of Research and Division of Gastroenterology and Hepatology, University Hospital Basel, Switzerland
    Search for more papers by this author
  • Markus H. Heim

    Corresponding author
    1. Department of Research and Division of Gastroenterology and Hepatology, University Hospital Basel, Switzerland
    • Division of Gastroenterology and Hepatology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
    Search for more papers by this author
    • fax: (41) 61-265-53-52


  • Potential conflict of interest: Nothing to report.

Abstract

Hepatitis C virus (HCV) infection is an important cause of chronic liver disease. Standard therapy, pegylated interferon α (pegIFNα) combined with ribavirin, results in a sustained response rate in approximately half of patients. The cause of treatment failure in the other half of the patients is unknown, but viral interference with IFNα signal transduction through the Jak-STAT pathway might be an important factor. We have shown previously that the expression of HCV proteins leads to an impairment of Jak-STAT signaling because of an inhibition of STAT1 methylation. Unmethylated STAT1 is less active because it can be bound and inactivated by its inhibitor, protein inhibitor of activated STAT1 (PIAS1). We show that treating cells with S-adenosyl-L-methionine (AdoMet) and betaine could restore STAT1 methylation and improve IFNα signaling. Furthermore, the antiviral effect of IFNα in cell culture could be significantly enhanced by the addition of AdoMet and betaine. In conclusion, we propose that the addition of these drugs to the standard therapy of patients with chronic hepatitis C could overcome treatment resistance. (HEPATOLOGY 2006;43:796–806.)

Ancillary