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. 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.
Gus'kova
Anna A
AA
Research Center for Medical Genetics, Russian Academy of Medical Sciences, Moskvorechie 1, Moscow 115478, Russia.
Skoblov
Mikhail Yu
MY
Korovina
Anna N
AN
Yasko
Maxim V
MV
Karpenko
Inna L
IL
Kukhanova
Marina K
MK
Andronova
Valeria L
VL
Galegov
George A
GA
Skoblov
Yuri S
YS
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D024882:Drug Resistance, Viral; D006564:Herpesviridae / Q000187:drug effects / Q000235:genetics*; D006566:Herpesviridae Infections / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells
D000998:Antiviral Agents; D013937:Thymidine Kinase; D000212:Acyclovir