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Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335213/ https://www.ncbi.nlm.nih.gov/pubmed/25561727 http://dx.doi.org/10.1074/jbc.M114.602649 |
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author | Royall, Elizabeth Doyle, Nicole Abdul-Wahab, Azimah Emmott, Ed Morley, Simon J. Goodfellow, Ian Roberts, Lisa O. Locker, Nicolas |
author_facet | Royall, Elizabeth Doyle, Nicole Abdul-Wahab, Azimah Emmott, Ed Morley, Simon J. Goodfellow, Ian Roberts, Lisa O. Locker, Nicolas |
author_sort | Royall, Elizabeth |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4335213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-43352132015-02-27 Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection Royall, Elizabeth Doyle, Nicole Abdul-Wahab, Azimah Emmott, Ed Morley, Simon J. Goodfellow, Ian Roberts, Lisa O. Locker, Nicolas J Biol Chem Microbiology 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. American Society for Biochemistry and Molecular Biology 2015-02-20 2015-01-05 /pmc/articles/PMC4335213/ /pubmed/25561727 http://dx.doi.org/10.1074/jbc.M114.602649 Text en © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version full access. Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/) applies to Author Choice Articles |
spellingShingle | Microbiology Royall, Elizabeth Doyle, Nicole Abdul-Wahab, Azimah Emmott, Ed Morley, Simon J. Goodfellow, Ian Roberts, Lisa O. Locker, Nicolas Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection |
title | Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection |
title_full | Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection |
title_fullStr | Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection |
title_full_unstemmed | Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection |
title_short | Murine Norovirus 1 (MNV1) Replication Induces Translational Control of the Host by Regulating eIF4E Activity during Infection |
title_sort | murine norovirus 1 (mnv1) replication induces translational control of the host by regulating eif4e activity during infection |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335213/ https://www.ncbi.nlm.nih.gov/pubmed/25561727 http://dx.doi.org/10.1074/jbc.M114.602649 |
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