This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services 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 Google Scholar Google Scholar Articles by Cinatl, J. Articles by Doerr, H. W. Search for Related Content PubMed PubMed Citation Articles by Cinatl, J., Jr. Articles by Doerr, H. W.

(American Journal of Pathology. 1999;155:285-292.)
© 1999 American Society for Investigative Pathology

Regular Articles

Human Cytomegalovirus Infection Decreases Expression of Thrombospondin-1 Independent of the Tumor Suppressor Protein p53

Jindrich Cinatl Jr.^*, Ruslan Kotchetkov^*, Martin Scholz^*, Jaroslav Cinatl, Jens-Uwe Vogel^*, Pablo Hernáiz Driever and Hans Wilhelm Doerr^*

From the Zentrum der Hygiene,^*
Institut für Medizinische Virologie, Zentrum für Kinderheilkunde und Jugendmedizin,
Abteilung Pädiatrische Hämatologie und Onkologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany, and Department of Neurosurgery,
Georgetown University Medical Center, Washington, D.C.

Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis. It has been shown that promoter sequences of the TSP-1 gene can be transactivated by the wild-type tumor suppressor protein p53. As human cytomegalovirus (HCMV) infection inactivates wild-type p53 of various cell types, we investigated whether HCMV infection is associated with reduced TSP-1 production. We found, in conjunction with accumulated p53, that TSP-1 mRNA and protein expression was significantly reduced in HCMV-infected cultured human fibroblasts. To determine whether the observed TSP-1 suppression depends on p53 inactivation, the p53-defective astrocytoma cell line U373MG was infected with HCMV. In these cells TSP-1 expression was also significantly reduced by HCMV infection whereas expression of the p53 mutant variant remained unaltered. In both cell lines the decreased expression of TSP-1 mRNA occurred early after infection (4 hours), indicating that HCMV inhibits TSP-1 transcription during the immediate-early phase of infection before HCMV DNA replication. Inhibition of HCMV DNA synthesis by ganciclovir did not influence TSP-1 reduction whereas the antisense oligonucleotide ISIS 2922, complementary to HCMV immediate-early mRNA, completely prevented the HCMV-mediated TSP-1 suppression. These findings strongly suggest a novel role for HCMV in the modulation of angiogenesis due to p53-independent down-regulation of TSP-1 expression.

This article has been cited by other articles:

				D. A. Mitchell, W. Xie, R. Schmittling, C. Learn, A. Friedman, R. E. McLendon, and J. H. Sampson Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma Neuro-oncol, February 1, 2008; 10(1): 10 - 18. [Abstract] [Full Text] [PDF]

				J. Cinatl Jr, M. Michaelis, C. Fleckenstein, G. Bauer, H. Kabickova, M. Scholz, H. F. Rabenau, and H. W. Doerr West Nile Virus Infection Induces Interferon Signalling in Human Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 645 - 651. [Abstract] [Full Text] [PDF]

				M. Michaelis, T. Suhan, A. Reinisch, A. Reisenauer, C. Fleckenstein, D. Eikel, H. Gumbel, H. W. Doerr, H. Nau, and J. Cinatl Jr Increased Replication of Human Cytomegalovirus in Retinal Pigment Epithelial Cells by Valproic Acid Depends on Histone Deacetylase Inhibition Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3451 - 3457. [Abstract] [Full Text] [PDF]

				C. S. Cobbs, L. Harkins, M. Samanta, G. Y. Gillespie, S. Bharara, P. H. King, L. B. Nabors, C. G. Cobbs, and W. J. Britt Human Cytomegalovirus Infection and Expression in Human Malignant Glioma Cancer Res., June 1, 2002; 62(12): 3347 - 3350. [Abstract] [Full Text] [PDF]

				E. Fosslien Molecular Pathology of Cyclooxygenase-2 in Cancer-induced Angiogenesis Ann. Clin. Lab. Sci., October 1, 2001; 31(4): 325 - 348. [Abstract] [Full Text] [PDF]

				J. Cinatl Jr, S. Margraf, J.-U. Vogel, M. Scholz, J. Cinatl, and H. W. Doerr Human Cytomegalovirus Circumvents NF-{kappa}B Dependence in Retinal Pigment Epithelial Cells J. Immunol., August 15, 2001; 167(4): 1900 - 1908. [Abstract] [Full Text] [PDF]

				B. Detrick, C. N. Nagineni, L. R. Grillone, K. P. Anderson, S. P. Henry, and J. J. Hooks Inhibition of Human Cytomegalovirus Replication in a Human Retinal Epithelial Cell Model by Antisense Oligonucleotides Invest. Ophthalmol. Vis. Sci., January 1, 2001; 42(1): 163 - 169. [Abstract] [Full Text]

				J. Cinatl Jr., R. Blaheta, M. Bittoova, M. Scholz, S. Margraf, J.-U. Vogel, J. Cinatl, and H. W. Doerr Decreased Neutrophil Adhesion to Human Cytomegalovirus-Infected Retinal Pigment Epithelial Cells Is Mediated by Virus-Induced Up-Regulation of Fas Ligand Independent of Neutrophil Apoptosis J. Immunol., October 15, 2000; 165(8): 4405 - 4413. [Abstract] [Full Text] [PDF]