HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Fairley, J. A. Articles by Sinclair, J. H. Search for Related Content PubMed PubMed Citation Articles by Fairley, J. A. Articles by Sinclair, J. H. Agricola Articles by Fairley, J. A. Articles by Sinclair, J. H.

Human cytomegalovirus infection inhibits epidermal growth factor (EGF) signalling by targeting EGF receptors

Department of Medicine, University of Cambridge, Level 5, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK¹
Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow, UK²

Author for correspondence: John Sinclair. Fax +44 1223 336846. e-mail js{at}mole.bio.cam.ac.uk

Infection with human cytomegalovirus (HCMV) is known to involve complex interactions between viral and cellular factors resulting in perturbation of a number of cellular functions. Specifically, HCMV infection targets control of the cell cycle, cellular transcription and immunoregulation, presumably to optimize the cellular environment for virus persistence and productive infection. Here, we show that HCMV infection also prevents external signalling to the cell by disrupting the function of epidermal growth factor receptor (EGFR). Infection with HCMV resulted in a decrease in cell-surface expression of EGFR. This decrease was correlated with a concomitant decrease in steady-state levels of EGFR protein. Consistent with this, HCMV inhibited EGF-mediated receptor autophosphorylation. Infection with a mutant HCMV deleted of all viral gene products known to be involved in down-regulation of MHC Class I receptors still resulted in this down-regulation, implying that EGFR down-regulation by HCMV is mediated by a novel virus function. We suggest that a primary goal of HCMV is to ‘isolate’ the infected cell from host-mediated signals so that the cell responds solely to an array of virus-specific signals which optimize the cell for virus production.

This article has been cited by other articles:

				I. Jafferji, M. Bain, C. King, and J. H. Sinclair Inhibition of epidermal growth factor receptor (EGFR) expression by human cytomegalovirus correlates with an increase in the expression and binding of Wilms' Tumour 1 protein to the EGFR promoter J. Gen. Virol., July 1, 2009; 90(7): 1569 - 1574. [Abstract] [Full Text] [PDF]

				M. K. Isaacson, A. L. Feire, and T. Compton Epidermal Growth Factor Receptor Is Not Required for Human Cytomegalovirus Entry or Signaling J. Virol., June 15, 2007; 81(12): 6241 - 6247. [Abstract] [Full Text] [PDF]

				C. A. King, J. Baillie, and J. H. Sinclair Human cytomegalovirus modulation of CCR5 expression on myeloid cells affects susceptibility to human immunodeficiency virus type 1 infection. J. Gen. Virol., August 1, 2006; 87(Pt 8): 2171 - 2180. [Abstract] [Full Text] [PDF]

				M. Leis, M. Marschall, and T. Stamminger Downregulation of the cellular adhesion molecule Thy-1 (CD90) by cytomegalovirus infection of human fibroblasts J. Gen. Virol., July 1, 2004; 85(7): 1995 - 2000. [Abstract] [Full Text] [PDF]

				L. M. Maglova, W. E. Crowe, and J. M. Russell Perinuclear localization of Na-K-Cl-cotransporter protein after human cytomegalovirus infection Am J Physiol Cell Physiol, June 1, 2004; 286(6): C1324 - C1334. [Abstract] [Full Text] [PDF]

				J. Baillie, D. A. Sahlender, and J. H. Sinclair Human Cytomegalovirus Infection Inhibits Tumor Necrosis Factor Alpha (TNF-{alpha}) Signaling by Targeting the 55-Kilodalton TNF-{alpha} Receptor J. Virol., June 15, 2003; 77(12): 7007 - 7016. [Abstract] [Full Text] [PDF]