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PMID: 15016848 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro.

Journal of virology ·Vol. 78 ·No. 7 ·2004-04-00 ·Pages 3271-8

Gradi A, Foeger N, Strong R, Svitkin YV, Sonenberg N, Skern T, Belsham GJ

Abstract

Foot-and-mouth disease virus (FMDV) induces a very rapid inhibition of host cell protein synthesis within infected cells. This is accompanied by the cleavage of the eukaryotic translation initiation factor 4GI (eIF4GI). The cleavage of the related protein eIF4GII has now been analyzed. Within FMDV-infected cells, cleavage of eIF4GI and eIF4GII occurs with similar kinetics. Cleavage of eIF4GII is induced in cells and in cell extracts by the FMDV leader protease (L(pro)) alone, generating cleavage products similar to those induced by enterovirus and rhinovirus 2A protease (2A(pro)). By the use of a fusion protein containing residues 445 to 744 of human eIF4GII, it was demonstrated that the FMDV L(pro) specifically cleaves this protein between residues G700 and S701, immediately adjacent to the site (V699/G700) cleaved by rhinovirus 2A(pro) in vitro. The G700/S701 cleavage site does not correspond, by amino acid sequence alignment, to that cleaved in eIF4GI by the FMDV L(pro) in vitro. Knowledge of the cleavage sites and the three-dimensional structures of the FMDV L(pro) and rhinovirus 2A(pro) enabled mutant forms of the eIF4GII sequence to be generated that are differentially resistant to either one of these proteases. These results confirmed the specificity of each protease and showed that the mutant forms of the fusion protein substrate retained their correct sensitivity to other proteases.

MeSH Terms

Amino Acid Sequence Animals Binding Sites Cell Line Cricetinae Endopeptidases/genetics,metabolism Eukaryotic Initiation Factor-4G Foot-and-Mouth Disease Virus/enzymology,genetics,physiology Humans Molecular Sequence Data Mutation Peptide Fragments/metabolism Peptide Initiation Factors/genetics,metabolism Substrate Specificity

Chemicals

EIF4G1 protein, human EIF4G2 protein, human Eukaryotic Initiation Factor-4G Peptide Fragments Peptide Initiation Factors Endopeptidases leader proteinase, foot-and-mouth disease virus

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Gradi Alessandra

Institute for Animal Health, Pirbright, Woking, Surrey GU24 0NF, United Kingdom. graham.belsham@bbsrc.ac.uk

Foeger Nicole

Strong Rebecca

Svitkin Yuri V

Sonenberg Nahum

Skern Tim

Belsham Graham J

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Article Info

Journal

Journal of virology

Abbr.

J Virol

ISSN

0022-538X

DOI

10.1128/jvi.78.7.3271-3278.2004

graham.belsham@bbsrc.ac.uk

Published

2004-04-00

Pages

3271-8

Language

English

Region

United States

NLM ID

0113724

PMCID

PMC371048

Subset

External Links

PubMed source DOI: 10.1128/jvi.78.7.3271-3278.2004 PMC Full Text View journal details

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Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro.

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