Characteristics of Herpesvirus Mutants Resistant to Phosphonoformate and Phosphonoacetate

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Abstract
Mutants of herpes simplex virus type 1, resistant to phosphonoformate (PFA) and phosphonoacetate (PAA), have been selected in cell culture. The PFA-resistant mutant (HSV-PFA r ) and the PAA-resistant mutant (HSV-PAA r ) were also resistant to PAA and PFA, respectively. This cross-resistance indicates that PFA and PAA interact at the same site. The HSV-PFA r had a decreased susceptibility to vidarabine, but no difference in sensitivity to idoxuridine (5-iodo-2′-deoxyuridine) was observed when compared to the wild type. The induced deoxyribonucleic acid polymerases isolated from cells infected with HSV-PFA r and HSV-PAA r were both cross-resistant to inhibition by PFA and PAA. No increased resistance to vidarabine triphosphate could be observed, but the susceptibility to inhibition by pyrophosphate was about two times lower. None of the mutants showed any increased temperature sensitivity