Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection

Jens M. Werner, Elisavet Serti, Xenia Chepa-Lotrea, Jonathan Stoltzfus, Golo Ahlenstiel, Mazen Noureddin, Jordan J. Feld, T. Jake Liang, Yaron Rotman, Barbara Rehermann

Research output: Contribution to journalArticle

Abstract

Ribavirin (RBV) is an important component of interferon (IFN)-based and direct antiviral treatment regimens for hepatitis C virus (HCV) infection. Immunomodulation, in particular improvement of the host IFN response, has been proposed as RBV's mechanism of action. Natural killer (NK) cells are sensitive biomarkers for IFN-α/β receptor signaling, as NK cell cytotoxicity and IFN-γ production are regulated by signal transducer and activator of transcription (STAT)1- and STAT4-phosphorylation, respectively. Specifically, pSTAT1-dependent NK cell cytotoxicity increases and pSTAT4-dependent IFN-γ production decreases in response to endogenous, virus-induced IFN-α and during IFN-α-based therapy. To assess whether RBV has a direct effect on NK cells and/or improves the IFN-γ response of NK cells in the presence of IFN-α, we prospectively studied 22 HCV patients with and 32 patients without 4 weeks of RBV pretreatment, who all received subsequent pegylated (Peg)IFN/ribavirin combination therapy. During RBV pretreatment, both the frequency of CD56dim NK cells with cytotoxic effector functions and the frequency of CD56bright NK cells with the capacity to produce IFN-γ decreased (P=0.049 and P=0.001, respectively). In vitro or in vivo exposure of NK cells to RBV improved the pSTAT4 (P

Original languageEnglish (US)
Pages (from-to)1160-1169
Number of pages10
JournalHepatology
Volume60
Issue number4
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

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Ribavirin
Virus Diseases
Natural Killer Cells
Hepacivirus
Interferons
Therapeutics
Interferon Receptors
STAT1 Transcription Factor
Immunomodulation
Antiviral Agents
Biomarkers
Phosphorylation
Viruses

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Werner, J. M., Serti, E., Chepa-Lotrea, X., Stoltzfus, J., Ahlenstiel, G., Noureddin, M., ... Rehermann, B. (2014). Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection. Hepatology, 60(4), 1160-1169. https://doi.org/10.1002/hep.27092

Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection. / Werner, Jens M.; Serti, Elisavet; Chepa-Lotrea, Xenia; Stoltzfus, Jonathan; Ahlenstiel, Golo; Noureddin, Mazen; Feld, Jordan J.; Liang, T. Jake; Rotman, Yaron; Rehermann, Barbara.

In: Hepatology, Vol. 60, No. 4, 01.10.2014, p. 1160-1169.

Research output: Contribution to journalArticle

Werner, JM, Serti, E, Chepa-Lotrea, X, Stoltzfus, J, Ahlenstiel, G, Noureddin, M, Feld, JJ, Liang, TJ, Rotman, Y & Rehermann, B 2014, 'Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection', Hepatology, vol. 60, no. 4, pp. 1160-1169. https://doi.org/10.1002/hep.27092
Werner JM, Serti E, Chepa-Lotrea X, Stoltzfus J, Ahlenstiel G, Noureddin M et al. Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection. Hepatology. 2014 Oct 1;60(4):1160-1169. https://doi.org/10.1002/hep.27092
Werner, Jens M. ; Serti, Elisavet ; Chepa-Lotrea, Xenia ; Stoltzfus, Jonathan ; Ahlenstiel, Golo ; Noureddin, Mazen ; Feld, Jordan J. ; Liang, T. Jake ; Rotman, Yaron ; Rehermann, Barbara. / Ribavirin improves the IFN-γ response of natural killer cells to IFN-based therapy of hepatitis C virus infection. In: Hepatology. 2014 ; Vol. 60, No. 4. pp. 1160-1169.
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