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J Biol Chem. 2014 Aug 1;289(31):21738-50. doi: 10.1074/jbc.M114.550657. Epub 2014 Jun 13.

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

Author information

1
From the Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.
2
From the Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
3
Department of Life Sciences, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
4
Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom, and.
5
From the Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom, Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom, and.
6
University of Surrey, Faculty of Health and Medical Sciences, School of Biosciences and Medicine, Guildford GU2 7HX, United Kingdom.
7
From the Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom, Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom, and ig299@cam.ac.uk.

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.

KEYWORDS:

Eukaryotic Translation Initiation Factor 4E (eIF4E); Norovirus; Plus-stranded RNA Virus; Translation; Translation Initiation Factor; VPg; Virus; eIF4G

PMID:
24928504
PMCID:
PMC4118132
DOI:
10.1074/jbc.M114.550657
[Indexed for MEDLINE]
Free PMC Article

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