DIFFERENT ANTIVIRAL POTENCIES OF BV-ARAU AND RELATED NUCLEOSIDE ANALOGS AGAINST HERPES-SIMPLEX VIRUS TYPE-1 IN HUMAN CELL-LINES AND VERO CELLS

Antiviral potencies against herpes simplex virus type 1 (HSV-1) of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) and ten other nucleoside analogues in human embryonic lung fibroblast (HEL) cells were compared with those in Vero cells. 5-Halogenovinylarabinosyluracils, highly active in HEL cells, were inactive against all three laboratory-stocked strains of HSV-1 but exerted moderate antiviral effects on three clinical isolates in Vero cells. The reduction in anti-HSV-1 potencies of other representative nucleoside analogues in Vero cells was much less than those of 5-halogenovinylarabinosyluracils. However, significant antiviral potencies of BV-araU against laboratory strains were observed in other human and monkey fibroblast cells including an immortalized cell line. Significant enhancement of antiviral activity of BV-araU against a laboratory strain and a clinical isolate was demonstrated in Vero cells by the addition of 0.1-mu-M aminopterin or FUdR, an inhibitor of thymidylate synthesis. The potentiated anti-HSV-1 activity in Vero cells was comparable to the potency in HEL cells without the inhibitor. These results suggested that high activity of thymidylate synthesis and a large thymidylate pool size in Vero cells seem to be related to loss of anti-HSV-1 potency of BV-araU. Original tissue type, species, and the immortality may not be responsible for the reduced antiviral activity of BV-araU in Vero cells.