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The Herpesvirus Encoded dUTPase as a Potential Chemotherapeutic Target

[ Vol. 2 , Issue. 4 ]

Author(s):

A. W. Studebaker, G. K. Balendiran and Marshall V. Williams   Pages 371 - 379 ( 9 )

Abstract:


The human herpesviruses are a well characterized group of viruses that are responsible for a wide spectrum of human diseases. Included in this group of pathogens are the alphaherpesviruses (herpes simplex types 1 and 2 and varicella-zoster virus), the betaherpesviruses (cytomegalovirus, human herpesvirus types 6 and 7) and the gammaherpesviruses (Epstein -Barr virus and human herpesvirus 8). An important feature of these viruses is that they cause latent infections that can be reactivated to cause disease. The herpesviruses encode for a large number of structural and non-structural proteins, and several of the non-structural proteins, such as thymidine kinase, DNA polymerase, and ribonucleotide reductase, have been utilized as targets for the development of anti-herpesvirus agents. Another herpesvirus encoded enzyme that has received little attention as a potential target for the development of specific anti-herpesvirus agents is deoxyuridine triphosphate nucleotidohydrolase (dUTPase). Furthermore, l ittle is known concerning the role of the herpesviruses encoded dUTPases in virus replication and in modulating the chemotherapeutic efficiency of other anti-herpes agents. Because of recent advances in molecular virology and biochemistry, it is now possible to rationally develop “designer” drugs based upon the structural / functional interaction of the drug with a specific viral protein. The purpose of this review is to describe previous studies demonstrating the potential use of the herpesvirus encoded dUTPase as a drug target, to describe problems associated with using the dUTPase as a target and to discuss new approaches that can be used.

Keywords:

anti-herpesvirus agents, (HSV-1 human herpesvirus 1), (HSV-2 human herpesvirus 2), varicella-zoster virus, human herpesvirus 3), Epstein-Barr virus, (EBV human herpesvirus4), human cytomegalovirus, (HCMV human herpesvirus 5), human herpesvirus 6 (HHV-6)

Affiliation:

Department of Molecular Virology, Immunology and Medical Genetics The Ohio State University, 2074 Graves Hall, 333 West 10th Ave., Columbus, OH 43210, USA



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