Initiation of protein synthesis by hepatitis C virus is refractory to reduced eIF2.GTP.Met-tRNA(i)(Met) ternary complex availability.

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 Cell

authors

Robert F,Kapp LD,Khan SN,Acker MG,Kolitz S,Kazemi S,Kaufman RJ,Merrick WC,Koromilas AE,Lorsch JR,Pelletier J

doi

10.1091/mbc.e06-06-0478

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

4632-44

issue

11

eissn

1059-1524

issn

1939-4586

pii

E06-06-0478

journal_volume

17

pub_type

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