Ribavirin regulates hepatitis C virus replication through enhancing interferon-stimulated genes and interleukin 8

The Journal of Infectious Diseases
Yoshio TokumotoMorikazu Onji

Abstract

The manner in which ribavirin (RBV) enhances the antiviral effects of interferon (IFN) against hepatitis C virus (HCV) remains unknown. We investigated whether RBV modifies IFN-stimulated genes (ISGs) in vivo and in vitro. We measured the messenger RNA (mRNA) levels of ISGs in T lymphocytes from patients with HCV infection who were receiving IFN-α therapy with or without RBV. We added RBV and/or IFN-α to a plasmid-based HCV replication system containing a full-length HCV genotype 1a sequence in HepG2 and Huh7 cell lines and the JFH-1 HCV genotype 2a sequence in Huh7 cell lines and measured levels of ISGs and autocrine IFN-β. The expression of protein kinase R and myxovirus resistance A mRNA was enhanced more with IFN-α and RBV than by IFN-α alone in assays in vivo and in vitro. Such enhancement depended on autocrine IFN-β being enhanced by RBV. RBV upregulated interleukin 8 (IL-8) in the absence of IFN-α. The IL-8 upregulation induced by RBV was responsible for the activation of activator protein 1 (AP-1). Ribavirin augments the anti-HCV effects of IFN-α induced by ISGs through enhancing autocrine IFN-β. Moreover, RBV can enhance IL-8 through activating AP-1. Improved understanding of ISG modulation by RBV would help to establi...Continue Reading

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Citations

Oct 18, 2012·The Journal of Infectious Diseases·Valérie MoalJean-Louis Mege
Aug 24, 2013·Hepatitis Monthly·Mojgan Noroozi KarimabadMohammad Kazemi Arababadi
Oct 23, 2015·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Wen-Wen ChouChia-Yen Dai
Jan 13, 2015·Cytokine & Growth Factor Reviews·Guido AntonelliEnrico Proietti
May 18, 2012·Antiviral Chemistry & Chemotherapy·Emmanuel ThomasT Jake Liang
Mar 5, 2020·Nucleosides, Nucleotides & Nucleic Acids·Alexander N PrutkovYulia V Berezovskaya

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