A single amino acid variation in the equine herpesvirus type 1 (EHV-1) DNA polymerase (Pol) (D752/N752) determines its neuropathogenic potential. Here, an EHV-1 strain RacL11 mutant with a deletion of Pol residue 752 was constructed. The deletion virus was then repaired to encode D752 or N752, respectively. The Δ752 mutant virus replicated with kinetics indistinguishable from those of D752 and N752 viruses. In addition, we could demonstrate that the deletion mutant was significantly more resistant to aphidicolin, a drug targeting Pol, compared with the N752 but not the D752 variant. In equine peripheral blood mononuclear cells, no significant difference was detected between the mutants with respect to cellular tropism or virus replication. The results demonstrated that amino acid residue 752 in EHV-1 Pol is not required for virus growth, and that only the N752 mutation confers a drug-sensitive phenotype to the virus.


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