title: Alpha interferon inhibits translation mediated by the internal ribosome entry site of six different hepatitis C virus genotypes.
abstract: 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-alpha2b 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-alpha2b 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-alpha2b blocks IRES-mediated translation and this effect is the same among HCVs of other genotypes.
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Sidhartha
authors.initials: S
authors.lastname: Hazari
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Asha
authors.initials: A
authors.lastname: Patil
authors.affiliation: Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Virendra
authors.initials: V
authors.lastname: Joshi
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Sullivan
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Cesar D
authors.initials: CD
authors.lastname: Fermin
authors.affiliation: Department of Microbiology and Immunology, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Garry
authors.affiliation: Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Elliott
authors.affiliation: Department of Pathology and Laboratory Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Srikanta
authors.initials: S
authors.lastname: Dash
mesh_terms: D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000254:growth & development; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D007370:Interferon Type I / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D014176:Protein Biosynthesis / Q000187:drug effects*; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007370:Interferon Type I; D012261:Ribonucleoproteins