Inhibition of B virus (Macacine herpesvirus 1) by conventional and experimental antiviral compounds.
B virus infection of humans results in high morbidity and mortality in as many as 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 those of a group of experimental nucleoside analogs with known anti-herpes simplex virus activity. Four of the experimental drugs tested were 10- to 100-fold more potent inhibitors of B virus replication than conventional antiviral agents. Drug efficacies were similar for multiple B virus isolates tested, with variations within 2-fold of the median effective concentration (EC(50)) for each drug, and each EC(50) was considerably lower than those for B virus thymidine kinase (TK) mutants. We observed no differences in the viral TK amino acid sequence between B virus isolates from rhesus monkeys and those from human zoonoses. Differences in the TK protein sequence between 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 (2'-fluoro-5-ethyl-Ara-U) than of conventional antiviral drugs argues for its compassionate use in advanced human B virus infections.
Viral Immunology Center, Georgia State University, P.O. Box 4118, Atlanta, GA 30302, USA.
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Krug
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Schinazi
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Hilliard
D000212:Acyclovir / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D015774:Ganciclovir / Q000494:pharmacology; D005838:Genotype; D006568:Herpesvirus 1, Cercopithecine / Q000187:drug effects*; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D013937:Thymidine Kinase / Q000378:metabolism; D014709:Vero Cells; D014740:Vidarabine / Q000494:pharmacology; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D004279:DNA, Viral; D013937:Thymidine Kinase; D014740:Vidarabine; D015774:Ganciclovir; D000212:Acyclovir