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

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Jun 30

PMID 26121620

Citations 6

Authors

Yolaine Cavignac

Diana Lieber

Kerstin Laib Sampaio

Johannes Madlung

Tobias Lamkemeyer

Gerhard Jahn

Alfred Nordheim

Christian Sinzger

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

RNA Helicase DDX3: A Double-Edged Sword for Viral Replication and Immune Signaling.

Hernandez-Diaz T, Valiente-Echeverria F, Soto-Rifo R Microorganisms. 2021; 9(6).

PMID: 34204859 PMC: 8227550. DOI: 10.3390/microorganisms9061206.

Targeting host DEAD-box RNA helicase DDX3X for treating viral infections.

Winnard Jr P, Vesuna F, Raman V Antiviral Res. 2020; 185:104994.

PMID: 33301755 PMC: 9667528. DOI: 10.1016/j.antiviral.2020.104994.

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Puhach O, Ostermann E, Krisp C, Frascaroli G, Schluter H, Brinkmann M PLoS Pathog. 2020; 16(10):e1008546.

PMID: 33031466 PMC: 7575108. DOI: 10.1371/journal.ppat.1008546.

DEAD-box RNA Helicase DDX3: Functional Properties and Development of DDX3 Inhibitors as Antiviral and Anticancer Drugs.

Kukhanova M, Karpenko I, Ivanov A Molecules. 2020; 25(4).

PMID: 32102413 PMC: 7070539. DOI: 10.3390/molecules25041015.

Quantitative Proteomic Approach Identifies Vpr Binding Protein as Novel Host Factor Supporting Influenza A Virus Infections in Human Cells.

Sadewasser A, Paki K, Eichelbaum K, Bogdanow B, Saenger S, Budt M Mol Cell Proteomics. 2017; 16(5):728-742.

PMID: 28289176 PMC: 5417817. DOI: 10.1074/mcp.M116.065904.

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