The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.

While it is well established that human cytomegalovirus (HCMV) upregulates many cellular proteins and incorporates several of them into its virion, little is known about the functional relevance of such virus-host interactions. Two cellular proteins, Grb2 and DDX3, gained our interest as they appear...

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Main Authors: Yolaine Cavignac, Diana Lieber, Kerstin Laib Sampaio, Johannes Madlung, Tobias Lamkemeyer, Gerhard Jahn, Alfred Nordheim, Christian Sinzger
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4509573?pdf=render
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author Yolaine Cavignac
Diana Lieber
Kerstin Laib Sampaio
Johannes Madlung
Tobias Lamkemeyer
Gerhard Jahn
Alfred Nordheim
Christian Sinzger
author_facet Yolaine Cavignac
Diana Lieber
Kerstin Laib Sampaio
Johannes Madlung
Tobias Lamkemeyer
Gerhard Jahn
Alfred Nordheim
Christian Sinzger
author_sort Yolaine Cavignac
collection DOAJ
description While it is well established that human cytomegalovirus (HCMV) upregulates many cellular proteins and incorporates several of them into its virion, little is known about the functional relevance of such virus-host interactions. Two cellular proteins, Grb2 and DDX3, gained our interest as they appeared enriched in virion particles and this incorporation depended on the viral tegument protein pp65, suggesting a functional relevance. We therefore tested whether the level of these proteins is altered upon HCMV infection and whether they support viral replication. Immunoblotting analyses of cellular fractions showed increased levels of both proteins in infected cells with a maximum at 2 d p.i. and a reduction of the soluble Grb2 fraction. Knockdown of either gene by transfection of siRNAs reduced viral spread not only of the cell culture adapted HCMV strain TB40/E but also of recent clinical isolates. Apparently, Grb2 and DDX3 are proviral cellular factors that are upregulated in infected cells.
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spelling doaj.art-4e4287a5a0b84174a4b2b20959f14b112022-12-21T23:54:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01106e013161410.1371/journal.pone.0131614The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.Yolaine CavignacDiana LieberKerstin Laib SampaioJohannes MadlungTobias LamkemeyerGerhard JahnAlfred NordheimChristian SinzgerWhile it is well established that human cytomegalovirus (HCMV) upregulates many cellular proteins and incorporates several of them into its virion, little is known about the functional relevance of such virus-host interactions. Two cellular proteins, Grb2 and DDX3, gained our interest as they appeared enriched in virion particles and this incorporation depended on the viral tegument protein pp65, suggesting a functional relevance. We therefore tested whether the level of these proteins is altered upon HCMV infection and whether they support viral replication. Immunoblotting analyses of cellular fractions showed increased levels of both proteins in infected cells with a maximum at 2 d p.i. and a reduction of the soluble Grb2 fraction. Knockdown of either gene by transfection of siRNAs reduced viral spread not only of the cell culture adapted HCMV strain TB40/E but also of recent clinical isolates. Apparently, Grb2 and DDX3 are proviral cellular factors that are upregulated in infected cells.http://europepmc.org/articles/PMC4509573?pdf=render
spellingShingle Yolaine Cavignac
Diana Lieber
Kerstin Laib Sampaio
Johannes Madlung
Tobias Lamkemeyer
Gerhard Jahn
Alfred Nordheim
Christian Sinzger
The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.
PLoS ONE
title The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.
title_full The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.
title_fullStr The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.
title_full_unstemmed The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.
title_short The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.
title_sort cellular proteins grb2 and ddx3 are increased upon human cytomegalovirus infection and act in a proviral fashion
url http://europepmc.org/articles/PMC4509573?pdf=render
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