Resistance of herpes simplex virus to adenine arabinoside and E-5-(2-bromovinyl)-2'-deoxyuridine: a physical analysis.
The physical map limits of DNA sequences within the DNA polymerase locus of herpes simplex virus (HSV) type 1 that define resistance mutations to adenine arabinoside (ara-A) and E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) were determined. Intertypic recombinants between HSV types 1 and 2, generated by marker rescue of temperature-sensitive mutations, had genome structures determined by restriction endonuclease analysis and were used to show that the resistance mutation for ara-Ar-1 is closely linked to the resistance mutations for phosphonoacetic acid (paar-1) and acycloguanosine (acvr-1) within a region of 2.6 kilobase pairs (kbp) in the HSV DNA polymerase locus. The resistance mutation for bvdur-1 is defined by a 2.9-kbp region that overlaps with the region defining resistance to the other three drugs but that is transferred separately. The DNA polymerase locus also contains a 2.2-kbp region that maps adjacent to and to the left of the region defining the bvdur-1 mutation which can be transferred separately and defines a region determining the HSV-1-specific sensitivity to BVDU in a manner analogous to that to acyclovir.
D000212:Acyclovir; D001483:Base Sequence; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004279:DNA, Viral / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D004352:Drug Resistance, Microbial; D005814:Genes, Viral; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D009154:Mutation; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D011995:Recombination, Genetic; D018139:Simplexvirus / Q000187:drug effects* / Q000235:genetics; D014740:Vidarabine / Q000494:pharmacology*
D004279:DNA, Viral; C020235:brivudine; D006147:Guanine; D004259:DNA-Directed DNA Polymerase; D014740:Vidarabine; D001973:Bromodeoxyuridine; D010746:Phosphonoacetic Acid; D000212:Acyclovir