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J Biol Chem. 2015 Feb 20;290(8):4748-58. doi: 10.1074/jbc.M114.602649. Epub 2015 Jan 5.

Murine norovirus 1 (MNV1) replication induces translational control of the host by regulating eIF4E activity during infection.

Author information

1
From the University of Surrey, Faculty of Health and Medical Sciences, School of Biosciences and Medicine, Guildford GU2 7HX, United Kingdom.
2
the Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom, and.
3
the Department of Biochemistry and Molecular Biology, School of Life Sciences, University of Sussex, JMS Building, Brighton BN1 9RH, United Kingdom.
4
From the University of Surrey, Faculty of Health and Medical Sciences, School of Biosciences and Medicine, Guildford GU2 7HX, United Kingdom, n.locker@surrey.ac.uk.

Abstract

Protein synthesis is a tightly controlled process responding to several stimuli, including viral infection. As obligate intracellular parasites, viruses depend on the translation machinery of the host and can manipulate it by affecting the availability and function of specific eukaryotic initiation factors (eIFs). Human norovirus is a member of the Caliciviridae family and is responsible for gastroenteritis outbreaks. Previous studies on feline calicivirus and murine norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts to direct translation by hijacking the host protein synthesis machinery. Here we report that MNV1 infection modulates the MAPK pathway to activate eIF4E phosphorylation. Our results show that the activation of p38 and Mnk during MNV1 infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes to changes in the translational state of specific host mRNAs. We propose that global translational control of the host by eIF4E phosphorylation is a key component of the host-pathogen interaction.

KEYWORDS:

Eukaryotic Translation Initiation Factor 4E (eIF4E); Host-Pathogen Interaction; Mitogen-activated Protein Kinase (MAPK); Protein Synthesis; RNA Virus; Translation Control

PMID:
25561727
PMCID:
PMC4335213
DOI:
10.1074/jbc.M114.602649
[Indexed for MEDLINE]
Free PMC Article

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