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Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.


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Authors

Chung, Liliane 
Bailey, Dalan 
Leen, Eoin N 
Emmott, Edward P 
Chaudhry, Yasmin 

Abstract

Viruses have evolved a variety of mechanisms to usurp the host cell translation machinery to enable translation of the viral genome in the presence of high levels of cellular mRNAs. Noroviruses, a major cause of gastroenteritis in man, have evolved a mechanism that relies on the interaction of translation initiation factors with the virus-encoded VPg protein covalently linked to the 5' end of the viral RNA. To further characterize this novel mechanism of translation initiation, we have used proteomics to identify the components of the norovirus translation initiation factor complex. This approach revealed that VPg binds directly to the eIF4F complex, with a high affinity interaction occurring between VPg and eIF4G. Mutational analyses indicated that the C-terminal region of VPg is important for the VPg-eIF4G interaction; viruses with mutations that alter or disrupt this interaction are debilitated or non-viable. Our results shed new light on the unusual mechanisms of protein-directed translation initiation.

Description

Keywords

Eukaryotic Translation Initiation Factor 4E (eIF4E), Norovirus, Plus-stranded RNA Virus, Translation, Translation Initiation Factor, VPg, Virus, eIF4G, Base Sequence, Chromatography, Affinity, DNA Primers, Eukaryotic Initiation Factor-4G, Genome, Viral, Norovirus, Polymerase Chain Reaction, Protein Binding, Protein Biosynthesis, Proteomics, Viral Proteins

Journal Title

J Biol Chem

Conference Name

Journal ISSN

0021-9258
1083-351X

Volume Title

Publisher

Elsevier BV
Sponsorship
This work was supported by funding from the BBSRC (BB/I012303/1) and the Wellcome Trust (WT097997MA) to IG, funding from BBSRC to LR and NL (BB/I01232X/1), as well as to SC (BB/J001708/1). IG is a Wellcome Senior Fellow.