Antiviral and immunomodulatory activity of the metal chelator ethylenediaminedisuccinic acid against cytomegalovirus in vitro and in vivo.

作者: J.-U Vogel , M Michaelis , J Neyts , R.A Blaheta , R Snoeck

DOI: 10.1016/S0166-3542(02)00025-6

关键词: BiologyIn vitroEDDSVirologyIntercellular Adhesion Molecule-1Biological activityHuman cytomegalovirusGanciclovirCidofovirIn vivoPharmacology

摘要: Antiviral activity of the metal chelator ethylenediaminedisuccinic acid (EDDS) was examined in vitro against human cytomegalovirus (HCMV) wild type strains and that are resistant ganciclovir (GCV) cidofovir (HPMPC). EDDS inhibited replication wild-type as well GCV- HPMPC-resistant with a 50% effective concentration 7.4-12 microg/ml. At concentrations 100 microg/ml EDDS, unlike GCV or HPMPC, suppressed HCMV-induced up-regulation intercellular adhesion molecule-1 (ICAM-1) reduced T-cell to HCMV-infected cells monolayer model. In murine (MCMV) (EC50 8.6 microg/ml) caused mice some protection MCMV induced mortality at non-toxic dose. Since immunopathological factors may play significant role HCMV disease it will be interest further study whether is terms modulation inflammatory responses infections.

参考文章(42)
H. G�mbel, J. Cinatl Jr., J.-U. Vogel, M. Scholz, F. Hoffmann, H.F. Rabenau, F. Koch, H.W. Doerr, CMV Retinitis: Clinical Experience with the Metal Chelator Desferrioxamine Karger Publishers. ,vol. 21, pp. 173- 179 ,(1998) , 10.1159/000061698
J E Grundy, K L Downes, Up-regulation of LFA-3 and ICAM-1 on the surface of fibroblasts infected with cytomegalovirus Immunology. ,vol. 78, pp. 405- 412 ,(1993)
Thomas Spector, Joan A. Harrington, David J.T. Porter, Herpes and human ribonucleotide reductases: Inhibition by 2-acetylpyridine 5-[(2-chloroanilino)-thiocarbonyl]-thiocarbonohydrazone (348U87) Biochemical Pharmacology. ,vol. 42, pp. 91- 96 ,(1991) , 10.1016/0006-2952(91)90685-X
Douglas A. Jabs, Cheryl Enger, Michael Forman, J. P. Dunn, for The Cytomegalovirus Retinitis, Viral Resistance Study Group, Incidence of Foscarnet Resistance and Cidofovir Resistance in Patients Treated for Cytomegalovirus Retinitis Antimicrobial Agents and Chemotherapy. ,vol. 42, pp. 2240- 2244 ,(1998) , 10.1128/AAC.42.9.2240
S. Pr�sch, H.-D. Volk, P. Reinke, K. Pioch, W.-D. D�cke, D.-H. Kr�ger, Human Cytomegalovirus Infection in Transplant Recipients: Role of TNF-α for Reactivation and Replication of Human Cytomegalovirus Karger Publishers. ,vol. 21, pp. 29- 41 ,(1998) , 10.1159/000061688
J. Cinatl, M. Scholz, H. W. Doerr, H. F. Rabenau, CMV-Related Immunopathology S Karger AG. ,(1998)
G A Koretzky, E J Peterson, J T Ernest, R T Semnani, S C Patel, L Farrokh-Siar, K A Rezai, G A van Seventer, Human fetal retinal pigment epithelial cells induce apoptosis in the T-cell line Jurkat. Investigative Ophthalmology & Visual Science. ,vol. 40, pp. 1503- 1511 ,(1999)
J. Cinatl Jr., J.-U. Vogel, R. Kotchetkov, M. Scholz, H.W. Doerr, Proinflammatory Potential of Cytomegalovirus Infection Intervirology. ,vol. 42, pp. 419- 424 ,(1999) , 10.1159/000053980