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) An erratum has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions 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.

Human Cytomegalovirus Circumvents NF-B Dependence in Retinal Pigment Epithelial Cells¹

Jindrich Cinatl, Jr^2,*, Stefan Margraf^*, Jens-Uwe Vogel^*,, Martin Scholz, Jaroslav Cinatl^, and Hans Wilhelm Doerr^*

^* Zentrum der Hygiene, Institut für Medizinische Virologie, Zentrum für Kinderheilkunde und Jugendmedizin, Abteilung Pädiadrische Hämatologie und Onkologie, and Klinikum für Thorax-, Herz- und thorakale Gefächirurgie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany; and KlinLab, Prague, Czech Republic

The human CMV (HCMV) is a persistent virus that may cause severe inflammatory responses especially in immunocompromised hosts. In different cell types, HCMV infection leads to the activation of the pleiotropic transcription factor, NF-B, which triggers virus replication but also propagates cell-mediated inflammatory mechanisms that largely depend on PG synthesis. We investigated the interactions of HCMV and the NF-B-dependent PG synthesis pathway in cultures of retinal pigment epithelial (RPE) cells that are known to be infected in HCMV retinitis patients. Unlike in other cell types, HCMV increased neither NF-B activity nor p65 and p105/50 mRNA levels in RPE cells. Both TNF- and phorbol ester 12,0-tetradecanoylphorbol 13-acetate (TPA) enhanced NF-B activity but only TPA increased HCMV replication. Cyclooxygenase-2 expression and PGE₂ release was increased by TPA and TNF- but not by HCMV infection. Stimulatory activity of TPA on HCMV replication was suppressed by protein kinase C inhibitors and inhibitors of p42/44 and p38 mitogen-activated protein kinases but not by NF-B inhibitors. In conclusion, HCMV circumvents the NF-B route in favor of the protein kinase C-dependent mitogen-activated protein kinase pathway in RPE cells. This virus/host cell interaction might be a mechanism that promotes HCMV persistence in immune-privileged organs such as the eye.

This article has been cited by other articles:

				M. Michaelis, T. A. T. Ha, H. W. Doerr, and J. Cinatl Jr Valproic acid interferes with antiviral treatment in human cytomegalovirus-infected endothelial cells Cardiovasc Res, February 1, 2008; 77(3): 544 - 550. [Abstract] [Full Text] [PDF]

				M. Gustems, E. Borst, C. A. Benedict, C. Perez, M. Messerle, P. Ghazal, and A. Angulo Regulation of the Transcription and Replication Cycle of Human Cytomegalovirus Is Insensitive to Genetic Elimination of the Cognate NF-{kappa}B Binding Sites in the Enhancer J. Virol., October 1, 2006; 80(19): 9899 - 9904. [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]

				Y. H. Shen, L. Zhang, B. Utama, J. Wang, Y. Gan, X. Wang, J. Wang, L. Chen, G. M. Vercellotti, J. S. Coselli, et al. Human cytomegalovirus inhibits Akt-mediated eNOS activation through upregulating PTEN (phosphatase and tensin homolog deleted on chromosome 10) Cardiovasc Res, February 1, 2006; 69(2): 502 - 511. [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]

				D. Hargett, T. McLean, and S. L. Bachenheimer Herpes Simplex Virus ICP27 Activation of Stress Kinases JNK and p38 J. Virol., July 1, 2005; 79(13): 8348 - 8360. [Abstract] [Full Text] [PDF]

				M. Moutaftsi, P. Brennan, S. A. Spector, and Z. Tabi Impaired Lymphoid Chemokine-Mediated Migration due to a Block on the Chemokine Receptor Switch in Human Cytomegalovirus-Infected Dendritic Cells J. Virol., March 15, 2004; 78(6): 3046 - 3054. [Abstract] [Full Text] [PDF]

				C. A. Benedict, A. Angulo, G. Patterson, S. Ha, H. Huang, M. Messerle, C. F. Ware, and P. Ghazal Neutrality of the Canonical NF-{kappa}B-Dependent Pathway for Human and Murine Cytomegalovirus Transcription and Replication In Vitro J. Virol., January 15, 2004; 78(2): 741 - 750. [Abstract] [Full Text] [PDF]