AAC Accepts, published online ahead of print on 26 October 2009

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Antimicrob. Agents Chemother. doi:10.1128/AAC.01435-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Inhibition of B virus (Cercopithecine herpesvirus 1) by Conventional and Experimental Antiviral Compounds

P. W. Krug, R. F. Schinazi, and J. K. Hilliard^*

Viral Immunology Center, Georgia State University, and Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, Georgia

^* To whom correspondence should be addressed. Email: jhilliard{at}gsu.edu.

B virus infection of humans results in high morbidity and mortality in up to 80% of identified cases. The main objective of this study was to conduct a comparative analysis of conventional and experimental antiviral drug susceptibilities of B virus isolates from multiple macaque species and zoonotically infected humans. We used a plaque reduction assay to establish the effective inhibitory doses of acyclovir, ganciclovir, and vidarabine, as well as a group of experimental nucleoside analogs with known anti-herpes simplex virus activity. Four of the tested experimental drugs were 10 to 100-fold more potent inhibitors of B virus replication than conventional antiviral agents. Drug efficacy was similar for multiple B virus isolates tested with variations within 2-fold of the median effective concentration (EC₅₀) for each drug and was considerably lower than those of B virus TK mutants. We observed no differences in the viral thymidine kinase amino acid sequence between B virus isolates from rhesus monkeys and human zoonoses. Differences in the TK protein sequence of cynomolgus and pigtail macaque B virus isolates did not affect drug sensitivity except in the case of one compound. Taken together, these data suggest that future B virus zoonoses will respond consistently to conventional antiviral treatment. Further, the considerably higher potency of FEAU advocates its compassionate use in advanced human B virus infections.