DIFFERENTIAL AND SELECTIVE-INHIBITION OF CELLULAR AND HERPES-SIMPLEX VIRUS-DNA SYNTHESIS BY ARABINOFURANOSYLADENINE

The influence of 9-β-d-arabinofuranosyladenine (βaraAdo) and of its anomer 9-α-d-arabinofuranosyladenine (αaraAdo) was studied in non-infected cells and cells infected with herpes simplex virus type 1 (HSV-1) and HSV type 2 (HSV-2). αAraAdo is a strong inhibitor of proliferation of non-infected cells. Multiplication of HSV-1 and HSV-2 is not affected at all by αaraAdo, while their growth is strongly inhibited by βaraAdo. αAraAdo exerts no effect on the incorporation of dThd into HSV DNA, but blocks the incorporation into host cell DNA. Its anomer, βaraAdo, affects the incorporation rate of both the viral DNA system and the host cell DNA system (the latter one to a lesser extent). αAraAMP is incorporated into newly synthesized cellular DNA but not into HSV DNA. Enzymic studies relevant that αaraATP has no effect on the HSV DNA polymerase system but a high inhibitory potency in the host cell DNA polymerase α system. The anomeric form, βaraATP, is a sensitive inhibitor of HSV DNA polymerase while the cellular DNA polymerases α and β are more refractory. © 1979.