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

J Virol. 1982 Mar;41(3):909-18. doi: 10.1128/JVI.41.3.909-918.1982.


Mutants of herpes simplex virus type 1 resistant to the antiviral drug 9-beta-D-arabinofuranosyladenine (araA) have been isolated and characterized. AraA-resistant mutants can be isolated readily and appear at an appreciable frequency in low-passage 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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA-Directed DNA Polymerase / genetics*
  • Drug Resistance, Microbial
  • Genes, Viral
  • Mutation
  • Phosphonoacetic Acid / pharmacology
  • Simplexvirus / drug effects
  • Simplexvirus / enzymology
  • Simplexvirus / genetics*
  • Vidarabine / pharmacology*
  • Viral Proteins / genetics*


  • Viral Proteins
  • DNA-Directed DNA Polymerase
  • Vidarabine
  • Phosphonoacetic Acid