The multi-targeted kinase inhibitor sorafenib inhibits human cytomegalovirus replication

Michaelis, Martin and Paulus, Christina and Löschmann, 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. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1007/s00018-010-0510-8

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
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Sue Davies
Date Deposited: 08 Oct 2012 15:42
Last Modified: 30 Jan 2013 12:29
Resource URI: http://kar.kent.ac.uk/id/eprint/31391 (The current URI for this page, for reference purposes)
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