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

In this study, we continued to study antiherpetic properties of acyclovir 5¢-hydrogenphosphonate (Hp-ACV) in cell cultures and animal models. HpACV was shown to inhibit the development of herpetic infection in mice induced by the HSV-1 ⁄ L2 strain. The compound suppressed replication of both ACV-sensitive HSV-1 ⁄ L2 and ACV-resistant HSV-1 ⁄ L2 ⁄ R strains in Vero cell culture. Viral population resistant to Hp-ACV (HSV-1 ⁄ L2 ⁄ RHp-ACV) was developed much slower than ACV-resistant population. The analysis of Hp-ACV-resistant clones isolated from the HSV-1 ⁄ L2 ⁄ RHp-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 ⁄ L2 ⁄ RHp-ACV herpes virus thymidine kinase is shortened from the C-terminus by 100 amino acid residues in length.