Increased human cytomegalovirus replication in fibroblasts after treatment with therapeutical plasma concentrations of valproic acid.

Michaelis, Martin and Köhler, Nezira and Reinisch, Alexander and Eikel, Daniel and Gravemann, Ute and Doerr, Hans Wilhelm and Nau, Heinz and Cinatl, Jindrich (2004) Increased human cytomegalovirus replication in fibroblasts after treatment with therapeutical plasma concentrations of valproic acid. Biochemical Pharmacology, 68 (3). pp. 531-8. ISSN 0006-2952. (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

Abstract

Valproic acid (2-propylpentanoic acid, VPA), an effective inhibitor of histone deacetylases (HDAC) is used for the treatment of epilepsia. In this study, structure-activity relationships for the action of structurally modified VPA derivatives on human cytomegalovirus (HCMV) replication and HDAC inhibition were defined. Pretreatment of human foreskin fibroblasts with VPA (0.125-1mM) caused a concentration-dependent increase of HCMV immediate early and antigen late antigen expression. Structure-activity relationships of VPA derivatives for HCMV stimulation were compared to those for teratogenic action and those for HDAC inhibition. Side chain elongation and introduction of a triple bond in 4-position of the other chain caused teratogenicity, stimulated HCMV replication, and increased HDAC inhibition, as demonstrated by enhanced levels of acetylated histones. Teratogenic VPA derivatives with a branched chain in 3-position as well as a non-teratogenic anticonvulsive active VPA derivative did not stimulate HCMV or accumulation of acetylated histones. This demonstrates a strict correlation between inhibition of HDAC and increased HCMV replication.

Item Type:	Article
Subjects:	Q Science > QR Microbiology > QR355 Virology R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculties > Sciences > School of Biosciences
Depositing User:	Martin Michaelis
Date Deposited:	05 Jun 2013 20:19 UTC
Last Modified:	22 Apr 2014 14:10 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/34119 (The current URI for this page, for reference purposes)