Abstract
A cornerstone of the antiviral interferon response is phosphorylation of eukaryotic initiation factor (eIF)2α. This limits the availability of eIF2-GTP-Met-tRNAiMet ternary complexes, reduces formation of 43S preinitiation complexes, and blocks viral (and most cellular) mRNA translation. However, many viruses have developed counterstrategies that circumvent this cellular response. Herein, we characterize a novel class of translation initiation inhibitors that block ternary complex formation and prevent the assembly of 43S preinitiation complexes. We find that translation driven by the HCV IRES is refractory to inhibition by these compounds at concentrations that effectively block cap-dependent translation in vitro and in vivo. Analysis of initiation complexes formed on the HCV IRES in the presence of inhibitor indicates that eIF2α and Met-tRNAiMet are present, defining a tactic used by HCV to evade part of the antiviral interferon response.
Original language | English (US) |
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Pages (from-to) | 4632-4644 |
Number of pages | 13 |
Journal | Molecular biology of the cell |
Volume | 17 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2006 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology