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Thrombin induces Sp1-mediated antiviral effects in cytomegalovirus-infected human retinal pigment epithelial cells

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Abstract

Human cytomegalovirus (HCMV) retinitis causing retinal detachment and destruction of the blood-retina barrier is closely related to retinal hemorrhage/coagulation. However, the effects of procoagulants on HCMV (re)activation in retinal cells have not been investigated yet. Therefore, we studied whether thrombin modulates the expression of HCMV immediate early (IE) and late (L) genes in cultured human retinal pigment epithelial cells (RPE). Thrombin specifically stimulated the protease-activated receptor-1 (PAR-1) on RPE and, surprisingly, inhibited basal and 12,0-tetradecanoylphorbol 13-acetate-stimulated HCMV IE gene expression in infected RPE. On the other hand, HCMV strongly induced Sp1 DNA binding activity, which was prevented by thrombin/PAR1-mediated Sp1 hyperphosphorylation. Our data suggest that thrombin/PAR-1 may inhibit Sp1-dependent HCMV replication, which might be an important regulatory mechanism for HCMV persistence and replication in RPE.

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Acknowledgements

This work was supported in part by "Frankfurter Stiftung für krebskranke Kinder" and "Hilfe für krebskranke Kinder Frankfurt e.V."

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Authors and Affiliations

  1. Zentrum der Hygiene, Institut für Medizinische Virologie, Johann Wolfgang Goethe-Universität, Paul Ehrlich Str. 40, 60596, Frankfurt am Main, Germany

    Martin Scholz, Jens-Uwe Vogel, Gerold Höver, Ruslan Kotchetkov, Hans Wilhelm Doerr & Jindrich Cinatl Jr.

  2. Zentrum für Augenheilkunde, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany

    Frank Koch

  3. Institut für Virologie, Humboldt-Universität, Charité, Berlin, Germany

    Susanna Prösch

  4. KlinLab Prague, Prague, Czech Republic

    Jaroslav Cinatl

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  1. Martin Scholz
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  2. Jens-Uwe Vogel
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  4. Susanna Prösch
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  9. Jindrich Cinatl Jr.
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Correspondence to Jindrich Cinatl Jr..

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Scholz, M., Vogel, JU., Höver, G. et al. Thrombin induces Sp1-mediated antiviral effects in cytomegalovirus-infected human retinal pigment epithelial cells. Med Microbiol Immunol 193, 195–203 (2004). https://doi.org/10.1007/s00430-003-0194-x

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  • DOI: https://doi.org/10.1007/s00430-003-0194-x

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