Mutations in the herpes simplex virus DNA polymerase gene can confer resistance to 9-beta-D-arabinofuranosyladenine

D M Coen, P A Furman, P T Gelep, P A Schaffer
1982 Journal of Virology  
Mutants of herpes simplex virus type 1 resistant to the antiviral drug 9-4-Darabinofuranosyladenine (araA) have been isolated and characterized. AraAresistant mutants can be isolated readily and appear at an appreciable frequency in low-passsage stocks of wild-type virus. Of 13 newly isolated mutants, at least 11 were also resistant to phosphonoacetic acid (PAA). Of four previously described PAA-resistant mutants, two exhibited substantial araA resistance. The araA resistance phenotype of one
more » ... phenotype of one of these mutants, PAAr5, has been mapped to the HpaI-B fragment of herpes simplex virus DNA by marker transfer, and araA resistance behaved in marker transfer experiments as if it were closely linked to PAA resistance, a recognized marker for the viral DNA polymerase locus. PAAr5 induced viral DNA polymerase activity which was much less susceptible to inhibition by the triphosphate derivative of araA than was wild-type DNA polymerase. These genetic and biochemical data indicate that the herpes simplex virus DNA polymerase gene is a locus which, when mutated, can confer resistance to araA and thus that the herpes simplex virus DNA polymerase is a target for this antiviral drug.
doi:10.1128/jvi.41.3.909-918.1982 fatcat:xz27dm37zrashbtqzo7t6yrrn4