Michaelis, Martin and Paulus, Christina and Loeschmann, Nadine and Dauth, Stephanie and Stange, Elisabeth and Doerr, Hans Wilhelm and Nevels, Michael and Cinatl, Jindrich (2011) The multi-targeted kinase inhibitor sorafenib inhibits human cytomegalovirus replication. CELLULAR AND MOLECULAR LIFE SCIENCES, 68 (6). pp. 1079-1090. ISSN 1420-682X, 1420-9071
Full text not available from this repository. (Request a copy)Abstract
Human cytomegalovirus (HCMV) is a major pathogen in immunocompromised individuals. Here, non-toxic concentrations of the anti-cancer kinase inhibitor sorafenib were shown to inhibit replication of different HCMV strains (including a ganciclovir-resistant strain) in different cell types. In contrast to established anti-HCMV drugs, sorafenib inhibited HCMV major immediate early promoter activity and HCMV immediate early antigen (IEA) expression. Sorafenib is known to inhibit Raf. Comparison of sorafenib with the MEK inhibitor U0126 suggested that sorafenib inhibits HCMV IEA expression through inhibition of Raf but independently of signaling through the Raf downstream kinase MEK 1/2. In concordance, siRNA-mediated depletion of Raf but not of MEK-reduced IEA expression. In conclusion, sorafenib diminished HCMV replication in clinically relevant concentrations and inhibited HCMV IEA expression, a pathophysiologically relevant event that is not affected by established anti-HCMV drugs. Moreover, we demonstrated for the first time that Raf activation is involved in HCMV IEA expression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PIGMENT EPITHELIAL-CELLS; NF-KAPPA-B; VALPROIC ACID; TRANSPLANT RECIPIENTS; ANTIVIRAL TREATMENT; GENE-EXPRESSION; CANCER-PATIENTS; IN-VITRO; INFECTION; REACTIVATION; Human cytomegalovirus; Sorafenib; Kinase inhibitor; Raf; Immediate early antigen; Cancer chemotherapy; Oncomodulation; Antiviral therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Jun 2020 12:01 |
| Last Modified: | 25 Jun 2020 12:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21209 |
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