λ-Interferons and the single nucleotide polymorphisms: A milestone to tailor-made therapy for chronic hepatitis C

Authors

  • Yasuhito Tanaka,

    Corresponding author
    1. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya,
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  • Nao Nishida,

    1. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, and
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  • Masaya Sugiyama,

    1. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya,
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  • Katsushi Tokunaga,

    1. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, and
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  • Masashi Mizokami

    1. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya,
    2. Research Center for Hepatitis and Immunology, Kohnodai Hospital, National Center for Global Health and Medicine, Ichikawa, Japan
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Dr Yasuhito Tanaka, Department of Virology, Liver Unit, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya 467-8601, Japan. Email: ytanaka@med.nagoya-cu.ac.jp

Abstract

Type III interferons (IFN) (IFN-λ1, -λ2, -λ3/interleukin [IL]-29, -28A, -28B) are cytokines with type I IFN-like antiviral activities. Most cells have expressed both type I and III IFN following Toll-like receptor (TLR) stimulation or viral infection, whereas the ability of cells to respond to IFN-λ was restricted to a specific subset of cells. It was reported that signal transduction pathway of IFN-λ was similar to that of IFN-α/β although a receptor adapted by IFN-λ were distinct from that of IFN-α/β. However, the clinical significance and the role of each IFN-λ were unclear. Recent genome-wide association studies (GWAS) of the human whole genome revealed several single nucleotide polymorphism sites (SNP) strongly associated with the response to pegylated IFN-α (PEG-IFN) plus ribavirin (RBV) treatment in chronic hepatitis C patients. The SNP, which are located near the IL-28B gene of chromosome 19, were discovered simultaneously by three independent studies opening a new prospective in hepatitis C research. The present review highlights significant insights that can be derived from the GWAS approach, and summarizes current knowledge of in vitro and in vivo study on the role of IFN-λ in antiviral effect.

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