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

S Hazari, A Patil, V Joshi, DE Sullivan, CD Fermin, R Garry, Richard Michael Elliott, S Dash

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

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-alpha 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-alpha 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-alpha 2b blocks IRES-mediated translation and this effect is the same among HCVs of other genotypes.

Original languageEnglish
Pages (from-to)3047-3053
Number of pages7
JournalJournal of General Virology
Volume86
Issue number11
DOIs
Publication statusPublished - Nov 2005

Keywords

  • 5' UNTRANSLATED REGION
  • NECROSIS-FACTOR-ALPHA
  • PREDOMINANT GENOTYPE
  • SECONDARY STRUCTURE
  • CODING SEQUENCE
  • PLUS RIBAVIRIN
  • MESSENGER-RNA
  • UNITED-STATES
  • INFECTION
  • PROTEIN

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