Replication of equine herpesvirus type 1 and type 3: resistance to hydroxyurea and thymidine.
The replication of equine herpesvirus type 1 (EHV-1) and type 3 (EHV-3) was unimpeded in three different cell types-equine epithelial cells, equine fibroblasts, and mouse fibroblasts-which had been 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. However, 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 cesium chloride 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.
D000818:Animals; D002478:Cells, Cultured; D002500:Centrifugation, Isopycnic; D004279:DNA, Viral / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D006564:Herpesviridae / Q000187:drug effects*; D006736:Horses; D006918:Hydroxyurea / Q000494:pharmacology*; D013936:Thymidine / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D013936:Thymidine; D006918:Hydroxyurea