Influence of acyclovir and bucyclovir on nucleotide pools in cells infected with herpes simplex virus type 1

Abstract

The effects of the acyclic guanosine analogs acyclovir (ACV) and (R)-9-(3,4-dihydroxybutyl)guanine (bucyclovir, BCV) on the deoxyribonucleoside triphosphate (dNTP) pools of herpes simplex type 1 (HSV-1)-infected African green monkey kidney (GMK) and human embryonic lung fibroblast (HL) cells were investigated. HSV-1 infection increased the dNTP pools in both cell types compared with those in uninfected cells. Mock-infected GMK cells showed a 10-fold-higher dTTP concentration than comparable HL cells. ACV or BCV treatment of HSV-1-infected cells yielded further increases of the dNTP pools. ACV- or BCV-treated, HSV-1-infected HL cells showed 20- to 50-fold-higher concentrations of ACV triphosphate and BCV triphosphate, respectively, than similarly treated GMK cells. This is in accord with previous results, which showed that ACV and BCV are less active in GMK cells than in HL cells. This difference in activity is attributed to the substantial deoxythymidine pools previously found in GMK cells. The results are discussed in relation to known metabolic and kinetic parameters.