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Background and Aims ： Genetic variation in the IL－28B （interleukin／ 28B ； interferon lambda 3） region hasbeen associated’with sustained virologic response （SVR） rates in patjents with chronic hepatitis C treatedwith peginterferQn一αand ribavirin． Howeverthe mechanisms by which polymorphisms in the］［L－28 Bgene region affect host antiviral responses are not well understood．Methods ： Using the HCV l b and 2a replicon systemwe compared the effects of IFN－Xs and IFN－ct onHCV RNA replicationThe anti－HCV effect of IFN－X 3 and IFN－ct in combination was also assessed．Changes in gene expression induced by IFN一λ3 and IFN一αwere compared using cDNA microarray analysis．Results：工FN－PLs at concentrations of 1 ng／ml or more exhibited concentration－and time－dependent HCVinhibitionIFN－X3 showed the strongest antiviral activity among the members of the IFN－X family． ln com－binationIFN－X3 and’IFN－or had a synergistic anti－HCV effect ； howeverno synergistic enhancement wasobserved for interferon一＄timulated response elemen／t （ISRE） activity or upregulation of interferon－stimulated genes （ISGs）． With respect to the time course of ISG upregulationthe pe・ak of IFN－X3－inducedgene expression occurred later and lasted longer than that induced by工FN一（x． In additionalthough thegenes upregulated by IFN－a and IFN－X3 were similar by microarray analysisinterferon stimulated geneexpression appeared early and was prolonged by combined administration of these two IFNs．Conc’lusions ： IFN－ct and IFN－X3 in combination showed synergistic anti－HCV activity in vitro． Differencesin time－dependent upregulation of these genes might contribute to the synergistic antiviral activity． |
