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Antiherpetic Properties of Acyclovir 5′‐Hydrogenphosphonate and the Mutation Analysis of Herpes Virus Resistant Strains

А. А. ГуськоваMikhail SkoblovAnna N. KorovinaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov str., Moscow 119991, RussiaMaxim V. YaskoEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov str., Moscow 119991, RussiaInna L. KarpenkoEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov str., Moscow 119991, RussiaMarina K. KukhanovaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov str., Moscow 119991, RussiaВ. Л. АндроноваIvanovskii Institute of Virology, Russian Academy of Medical Sciences, 16 Gamalei str., Moscow 123098, RussiaGeorge A. GalegovIvanovskii Institute of Virology, Russian Academy of Medical Sciences, 16 Gamalei str., Moscow 123098, RussiaYuri S. SkoblovShemyakin & Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya str, 16/10, Moscow, Russia

2009en

ABI

Annotatsiya

In this study, we continued to study antiherpetic properties of acyclovir 5'-hydrogenphosphonate (Hp-ACV) in cell cultures and animal models. Hp-ACV was shown to inhibit the development of herpetic infection in mice induced by the HSV-1/L(2) strain. The compound suppressed replication of both ACV-sensitive HSV-1/L(2) and ACV-resistant HSV-1/L(2)/R strains in Vero cell culture. Viral population resistant to Hp-ACV (HSV-1/L(2)/R(Hp-ACV)) was developed much slower than ACV-resistant population. The analysis of Hp-ACV-resistant clones isolated from the HSV-1/L(2)/R(Hp-ACV) population demonstrated their partial cross-resistance to ACV. The mutations determining the resistance of HSV-1 clones to Hp-ACV were partly overlapped with mutations defining ACV resistance but did not always coincide. HSV-1/L(2)/R(Hp-ACV) herpes virus thymidine kinase is shortened from the C-terminus by 100 amino acid residues in length.

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Identifikatorlar

DOI: 10.1111/j.1747-0285.2009.00874.x

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