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A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication

Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes. In poliovirus-infected cells, ER and Golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral RNA synthesis. Virus replication is inhibited by brefeldin A (BFA), impli...

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Autores principales: Belov, George A., Feng, Qian, Nikovics, Krisztina, Jackson, Catherine L., Ehrenfeld, Ellie
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581890/
https://www.ncbi.nlm.nih.gov/pubmed/19023417
http://dx.doi.org/10.1371/journal.ppat.1000216
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author Belov, George A.
Feng, Qian
Nikovics, Krisztina
Jackson, Catherine L.
Ehrenfeld, Ellie
author_facet Belov, George A.
Feng, Qian
Nikovics, Krisztina
Jackson, Catherine L.
Ehrenfeld, Ellie
author_sort Belov, George A.
collection PubMed
description Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes. In poliovirus-infected cells, ER and Golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral RNA synthesis. Virus replication is inhibited by brefeldin A (BFA), implicating some components(s) of the cellular secretory pathway in virus growth. Formation of characteristic vesicles induced by expression of viral proteins was not inhibited by BFA, but they were functionally deficient. GBF1, a guanine nucleotide exchange factor for the small cellular GTPases, Arf, is responsible for the sensitivity of virus infection to BFA, and is required for virus replication. Knockdown of GBF1 expression inhibited virus replication, which was rescued by catalytically active protein with an intact N-terminal sequence. We identified a mutation in GBF1 that allows growth of poliovirus in the presence of BFA. Interaction between GBF1 and viral protein 3A determined the outcome of infection in the presence of BFA.
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spelling pubmed-25818902008-11-21 A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication Belov, George A. Feng, Qian Nikovics, Krisztina Jackson, Catherine L. Ehrenfeld, Ellie PLoS Pathog Research Article Replication of many RNA viruses is accompanied by extensive remodeling of intracellular membranes. In poliovirus-infected cells, ER and Golgi stacks disappear, while new clusters of vesicle-like structures form sites for viral RNA synthesis. Virus replication is inhibited by brefeldin A (BFA), implicating some components(s) of the cellular secretory pathway in virus growth. Formation of characteristic vesicles induced by expression of viral proteins was not inhibited by BFA, but they were functionally deficient. GBF1, a guanine nucleotide exchange factor for the small cellular GTPases, Arf, is responsible for the sensitivity of virus infection to BFA, and is required for virus replication. Knockdown of GBF1 expression inhibited virus replication, which was rescued by catalytically active protein with an intact N-terminal sequence. We identified a mutation in GBF1 that allows growth of poliovirus in the presence of BFA. Interaction between GBF1 and viral protein 3A determined the outcome of infection in the presence of BFA. Public Library of Science 2008-11-21 /pmc/articles/PMC2581890/ /pubmed/19023417 http://dx.doi.org/10.1371/journal.ppat.1000216 Text en This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Belov, George A.
Feng, Qian
Nikovics, Krisztina
Jackson, Catherine L.
Ehrenfeld, Ellie
A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication
title A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication
title_full A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication
title_fullStr A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication
title_full_unstemmed A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication
title_short A Critical Role of a Cellular Membrane Traffic Protein in Poliovirus RNA Replication
title_sort critical role of a cellular membrane traffic protein in poliovirus rna replication
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2581890/
https://www.ncbi.nlm.nih.gov/pubmed/19023417
http://dx.doi.org/10.1371/journal.ppat.1000216
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