Field H J, Anderson J R, Efstathiou S
J Gen Virol. 1984 Apr;65 ( Pt 4):707-19. doi: 10.1099/0022-1317-65-4-707.
Mice with established herpes encephalitis were used to compare the effects of chemotherapy using three different nucleoside analogues. Encephalitis was produced by intranasal inoculation of a type 1 strain of herpes simplex virus. Without chemotherapy all mice died within 5 to 7 days of inoculation. Oral acyclovir (ACV) was a successful preventative measure if commenced within 2 days of inoculation but much less effective if the onset of treatment was further delayed. From the third day, when central nervous system infection had definitely become established, ACV only reduced mortality if given intraperitoneally (i.p.) at regular 6-hourly intervals. Comparison with bromovinyldeoxyuridine (BVdU) and the new nucleoside analogue dihydroxypropoxymethylguanine (DHPG) using the same 6-hourly i.p. regimen revealed that BVdU was poorly effective, despite better activity in vitro, whereas DHPG was the most successful. Virus was rapidly eradicated from all parts of the brain by DHPG therapy, and by day 10, no infectious virus remained in the brains of treated mice, no virus antigens were observed and no trace of virus DNA could be detected in neural tissues by Southern blotting.
利用已患疱疹性脑炎的小鼠来比较三种不同核苷类似物化疗的效果。通过鼻内接种单纯疱疹病毒1型毒株引发脑炎。若不进行化疗，所有小鼠在接种后5至7天内死亡。口服阿昔洛韦（ACV）若在接种后2天内开始使用是一种成功的预防措施，但如果治疗开始时间进一步推迟则效果要差得多。从第三天起，当中枢神经系统感染已明确确立时，ACV只有以每6小时一次的间隔腹腔内给药（i.p.）才能降低死亡率。使用相同的每6小时一次腹腔内给药方案与溴乙烯脱氧尿苷（BVdU）和新核苷类似物二羟基丙氧基甲基鸟嘌呤（DHPG）进行比较发现，尽管BVdU在体外活性较好，但效果不佳，而DHPG最为成功。通过DHPG治疗，病毒迅速从大脑所有部位清除，到第10天，治疗小鼠的大脑中没有残留感染性病毒，未观察到病毒抗原，通过Southern印迹法在神经组织中也检测不到病毒DNA痕迹。
