Abstract:
:A cornerstone of the antiviral interferon response is phosphorylation of eukaryotic initiation factor (eIF)2alpha. This limits the availability of eIF2.GTP.Met-tRNA(i)(Met) 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 eIF2alpha and Met-tRNA(i)(Met) are present, defining a tactic used by HCV to evade part of the antiviral interferon response.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Robert F,Kapp LD,Khan SN,Acker MG,Kolitz S,Kazemi S,Kaufman RJ,Merrick WC,Koromilas AE,Lorsch JR,Pelletier Jdoi
10.1091/mbc.e06-06-0478subject
Has Abstractpub_date
2006-11-01 00:00:00pages
4632-44issue
11eissn
1059-1524issn
1939-4586pii
E06-06-0478journal_volume
17pub_type
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