IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection.

ABSTRACT: Genetic polymorphisms in IFNL4 have been shown to predict responses to IFN-α-based therapy in hepatitis C virus (HCV)-infected patients. The IFNL4-ΔG genotype, which encodes functional IFN-λ4 protein, is associated with a poor treatment response. In the present study, we investigated the induction and biological effects of IFN-λ4 in HCV-infected hepatocytes and their association with responsiveness to IFN-α. We also studied the effects of direct-acting antiviral (DAA) treatment on IFN-λ4 expression and IFN-α responsiveness. HCV infection induced IFN-λ4 expression at mRNA and protein levels in primary human hepatocytes (PHHs). In hepatoma cells, IFNL4 gene transfection or recombinant IFN-λ4 protein treatment robustly increased the protein levels of ISG15 and USP18 in an IFNLR1-dependent man

SUBMITTER: Sung PS 

PROVIDER: S-EPMC5476576 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature