Replication of Equine Herpesvirus Type 1 and Type 3: Resistance to Hydroxyurea and Thymidine

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Abstract
The replication of equine herpesvirus type 1 (EHV-1) and type 3 (EHV-3) was unimpeded in 3 different cell types, equine epithelial cells, equine fibroblasts and mouse fibroblasts, which were blocked in their capacity to synthesize host DNA by 2.5 mM hydroxyurea (HU) or 2 mM thymidine (TdR). The rate of DNA synthesis in uninfected or equine herpesvirus-infected cells in the presence of HU or TdR was measured by pulse-labeling cell samples with a labeled DNA precursor at different times after infection. DNA synthesis in uninfected cultures was completely inhibited by both compounds. In cells infected with EHV-1 or EHV-3 and incubated in the presence of HU or TdR, a burst of DNA synthesis occurred which coincided in time with that of virus-specific DNA replication in infected cells without inhibitors. Analysis by CsCl isopycnic centrifugation confirmed that the DNA made in drug-treated, infected cells was viral. A possible mechanism of the HU and TdR resistance of the equine herpesviruses is the induction of a ribonucleotide reductase which is insensitive to inhibition by these compounds.