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 Reinhardt, B. Articles by Michel, D. Search for Related Content PubMed PubMed Citation Articles by Reinhardt, B. Articles by Michel, D. Agricola Articles by Reinhardt, B. Articles by Michel, D.

Upregulation of functionally active vascular endothelial growth factor by human cytomegalovirus

¹ Abteilung Virologie, Universitätsklinikum Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany
² Roche Diagnostics GmbH, Nonnenwald 2, 82372 Penzberg, Germany
³ Department of Plastic Surgery, University Hospital Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany

Correspondence
Thomas Mertens
thomas.mertens{at}medizin.uni-ulm.de

Human cytomegalovirus (HCMV) infection is known to modulate host gene expression and has been linked to the pathogenesis of vasculopathies; however, relevant pathomechanisms are still unclear. It was shown that HCMV infection leads to upregulation of vascular endothelial growth factor (VEGF) expression in human foreskin fibroblasts and coronary artery smooth muscle cells (SMC). Activation of VEGF transcription by HCMV infection was confirmed by transient-expression experiments, which revealed that a short promoter fragment, pLuc135 (–85 to +50), is sufficient for activation. Site-directed mutagenesis of Sp1-recognition sites within this fragment abolished the upregulation of transcription. Functional VEGF protein is released into the culture supernatant of infected SMC. Incubation of endothelial cells with supernatants from HCMV-infected SMC cultures induced upregulation of VEGF receptor-2 expression on endothelial cells, as well as a significant upregulation of DNA synthesis, implicating cell proliferation. The mean incline of DNA synthesis at 48 and 72 h post-infection was 148 and 197 %, respectively. Addition of neutralizing antibodies against VEGF completely abolished this effect. Supernatants from SMC cultures incubated with UV-inactivated virus induced a comparable effect. This virus-induced paracrine effect may represent a molecular mechanism for HCMV-induced pathogenesis, such as inflammatory vasculopathies, by inducing a proatherogenic phenotype in SMC.

This article has been cited by other articles:

				J. Dumortier, D. N. Streblow, A. V. Moses, J. M. Jacobs, C. N. Kreklywich, D. Camp, R. D. Smith, S. L. Orloff, and J. A. Nelson Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing J. Virol., July 1, 2008; 82(13): 6524 - 6535. [Abstract] [Full Text] [PDF]

				R. Sivakumar, N. Sharma-Walia, H. Raghu, M. V. Veettil, S. Sadagopan, V. Bottero, L. Varga, R. Levine, and B. Chandran Kaposi's Sarcoma-Associated Herpesvirus Induces Sustained Levels of Vascular Endothelial Growth Factors A and C Early during In Vitro Infection of Human Microvascular Dermal Endothelial Cells: Biological Implications J. Virol., February 15, 2008; 82(4): 1759 - 1776. [Abstract] [Full Text] [PDF]

				C. Sinzger, G. Hahn, M. Digel, R. Katona, K. L. Sampaio, M. Messerle, H. Hengel, U. Koszinowski, W. Brune, and B. Adler Cloning and sequencing of a highly productive, endotheliotropic virus strain derived from human cytomegalovirus TB40/E J. Gen. Virol., February 1, 2008; 89(2): 359 - 368. [Abstract] [Full Text] [PDF]

				B. Reinhardt, M. Winkler, P. Schaarschmidt, R. Pretsch, S. Zhou, B. Vaida, A. Schmid-Kotsas, D. Michel, P. Walther, M. Bachem, et al. Human cytomegalovirus-induced reduction of extracellular matrix proteins in vascular smooth muscle cell cultures: a pathomechanism in vasculopathies? J. Gen. Virol., October 1, 2006; 87(Pt 10): 2849 - 2858. [Abstract] [Full Text] [PDF]

				D. Maussang, D. Verzijl, M. van Walsum, R. Leurs, J. Holl, O. Pleskoff, D. Michel, G. A. M. S. van Dongen, and M. J. Smit Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis PNAS, August 29, 2006; 103(35): 13068 - 13073. [Abstract] [Full Text] [PDF]

				G. Frascaroli, S. Varani, B. Moepps, C. Sinzger, M. P. Landini, and T. Mertens Human cytomegalovirus subverts the functions of monocytes, impairing chemokine-mediated migration and leukocyte recruitment. J. Virol., August 1, 2006; 80(15): 7578 - 7589. [Abstract] [Full Text] [PDF]