[lambda]-Interferons and the single nucleotide polymorphisms: A milestone to tailor-made therapy for chronic hepatitis C.
Tanaka, Yasuhito 1; Nishida, Nao 2; Sugiyama, Masaya 1; Tokunaga, Katsushi 2; Mizokami, Masashi 1,3
[Review]
Hepatology Research.
40(5):449-460, May 2010.
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: Type III interferons (IFN) (IFN-[lambda]1, -[lambda]2, -[lambda]3/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-[lambda] was restricted to a specific subset of cells. It was reported that signal transduction pathway of IFN-[lambda] was similar to that of IFN-[alpha]/[beta] although a receptor adapted by IFN-[lambda] were distinct from that of IFN-[alpha]/[beta]. However, the clinical significance and the role of each IFN-[lambda] 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-[alpha] (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-[lambda] in antiviral effect.
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