The Herpesvirus Encoded dUTPase as a Potential Chemotherapeutic Target

A.   W.   Studebaker; G.   K.   Balendiran; Marshall   V.   Williams

doi:10.2174/1389203013380946

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)