title: The Cellular Proteins Grb2 and DDX3 Are Increased upon Human Cytomegalovirus Infection and Act in a Proviral Fashion.
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.
authors.affiliation: Institute of Medical Virology and Epidemiology of Virus Diseases, University of Tübingen, Tübingen, Germany.
authors.forename: Yolaine
authors.initials: Y
authors.lastname: Cavignac
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Lieber
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Laib Sampaio
authors.affiliation: Proteome Center, University of Tübingen, Tübingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Madlung
authors.affiliation: Proteome Center, University of Tübingen, Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Lamkemeyer
authors.affiliation: Institute of Medical Virology and Epidemiology of Virus Diseases, University of Tübingen, Tübingen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Jahn
authors.affiliation: Proteome Center, University of Tübingen, Tübingen, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Nordheim
authors.affiliation: Institute of Virology, University of Ulm, Ulm, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Sinzger
mesh_terms: D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000378:metabolism* / Q000821:virology*; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D011533:Proviruses / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000378:metabolism; D014771:Virion; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D051380:GRB2 Adaptor Protein; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases