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.