1887

Abstract

ISG15 has recently been reported to possess antiviral properties against viruses, both and . Knock-down of ISG15 gene expression by small interfering RNA followed by alpha interferon (IFN-) treatment in Huh-7 cells resulted in an increased phenotypic sensitivity to IFN-, as determined by measuring hepatitis C virus (HCV) RNA replication inhibition in stably transfected HCV replicon cells and in cells infected with genotype 1a HCVcc (infectious HCV). This IFN--specific effect, which was not observed with IFN-, correlated with an increase in expression of the IFN--inducible genes IFI6, IFITM3, OAS1 and MX1, whereas the expression of the non-IFN--inducible genes PTBP-1 and JAK1 remained unchanged. It has previously been reported that, unlike ISG15 knock-down, increased sensitivity to IFN- after knock-down of USP18 occurs through the prolonged phosphorylation of STAT-1. Combination knock-down of ISG15 and USP18 resulted in a moderate increase in IFN--inducible gene expression compared with single ISG15 or USP18 knock-down. Furthermore, the phenotype of increased gene expression after ISG15 knock-down and IFN- treatment was also observed in non-hepatic cell lines A549 and HeLa. Taken together, these results reveal a novel function for ISG15 in the regulation of the IFN- pathway and its antiviral effect.

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2009-12-01
2021-10-22
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