Different antiviral potencies of BV-araU and related nucleoside analogues 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 microM 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.
Machida
H
H
Biology Laboratory, R & D Division, Yamasa Shoyu Co., Ltd., Chiba, Japan.
Nishitani
M
M
Suzutani
T
T
Hayashi
K
K
D000630:Aminopterin / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D004347:Drug Interactions; D005467:Floxuridine / Q000494:pharmacology; D006801:Humans; D009705:Nucleosides / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects*; D013936:Thymidine / Q000494:pharmacology; D014709:Vero Cells
D000998:Antiviral Agents; D009705:Nucleosides; D005467:Floxuridine; D001086:Arabinofuranosyluracil; C031368:sorivudine; D000630:Aminopterin; D013936:Thymidine