title: Norovirus translation requires an interaction between the C Terminus of the genome-linked viral protein VPg and eukaryotic translation initiation factor 4G.
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.
authors.affiliation: From the Section of Virology, Department of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom.
authors.forename: Liliane
authors.initials: L
authors.lastname: Chung
authors.affiliation: 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.
authors.forename: Dalan
authors.initials: D
authors.lastname: Bailey
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Eoin N
authors.initials: EN
authors.lastname: Leen
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom, and.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Emmott
authors.affiliation: 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.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Chaudhry
authors.affiliation: University of Surrey, Faculty of Health and Medical Sciences, School of Biosciences and Medicine, Guildford GU2 7HX, United Kingdom.
authors.forename: Lisa O
authors.initials: LO
authors.lastname: Roberts
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Curry
authors.affiliation: University of Surrey, Faculty of Health and Medical Sciences, School of Biosciences and Medicine, Guildford GU2 7HX, United Kingdom.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Locker
authors.affiliation: 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.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Goodfellow
mesh_terms: D001483:Base Sequence; D002846:Chromatography, Affinity; D017931:DNA Primers; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism*; D016679:Genome, Viral; D029322:Norovirus / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D014176:Protein Biosynthesis; D040901:Proteomics; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D017931:DNA Primers; D039603:Eukaryotic Initiation Factor-4G; D014764:Viral Proteins
keywords: Eukaryotic Translation Initiation Factor 4E (eIF4E); Norovirus; Plus-stranded RNA Virus; Translation; Translation Initiation Factor; VPg; Virus; eIF4G