Isolation of equine herpesvirus-1 mutants in the presence of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine: demonstration of resistance in vitro and in vivo.
The compound (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) had been previously shown to be highly effective in treatment of EHV-1 in a murine model for the equine disease. This paper describes the isolation of a series of mutants resistant to the drug. Resistance was demonstrated in cell culture and one mutant was tested in a murine model. The resistant mutant was pathogenic for mice; infectious virus was recovered from respiratory tissues and blood at levels similar to the parental virus. However, the mutant showed a significant degree of resistance in vivo, thus proving the virus-specific mode of action of the antiviral compound.
Field
H J
HJ
Department of Clinical Veterinary Medicine, University of Cambridge, U.K.
Awan
A R
AR
de la Fuente
R
R
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D004352:Drug Resistance, Microbial; D005260:Female; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000382:microbiology*; D004861:Herpesvirus 1, Equid / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010641:Phenotype
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D000225:Adenine