Alpha interferon inhibits translation mediated by the internal ribosome entry site of six different hepatitis C virus genotypes

1 Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA 2 Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA 3 Department of Microbiology and Immunology, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA 4 Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK Correspondence Srikanta Dash sdash{at}tulane.edu Certain genotypes of hepatitis C virus (HCV) respond less often than others to treatment with interferon (IFN). The mechanisms for this differential response are not known. In this report antiviral effects of IFN- 2b on translation were examined in a hepatic cell line using chimeric clones of internal ribosome entry site (IRES) sequences from six different HCV genotypes and the green fluorescence protein (GFP) gene. As a control, IFN action at the level of the IRES was examined in the presence of different cytokines. It was determined that IFN- 2b specifically inhibited the translation of GFP mediated by IRES sequences from six major HCV genotypes in a concentration-dependent manner. Other cytokines including tumour necrosis factor alpha, transforming growth factor beta 1, interleukin 1 and interleukin 6 have no inhibitory effect. The inhibition of translation in these experiments was not due to extensive intracellular degradation of IRES-GFP mRNA. These results suggest that the antiviral action of IFN- 2b blocks IRES-mediated translation and this effect is the same among HCVs of other genotypes. A table of expression data, and two figures showing a ribonuclease protection assay and flow analysis of GFP expression are available as supplementary material in JGV Online.