Denis J, Langlois M, Elkaim M, Amiel C, Aymard M, Huraux J M
Curr Eye Res. 1987 Jan;6(1):39-45. doi: 10.3109/02713688709020066.
The effects of repeated topical idoxuridine (IDU) administration of HSV1 strain sensitivity were investigated during 6 serial passages (P1 to P6) in the rabbit. By comparison to placebo treated rabbits, a delay in ulcer cicatrization appeared at P2 and clinical resistance was completed at P3. Clinical cross resistance to acyclovir (ACV) was also tested and demonstrated at P7. In vitro, a plaque reduction test on Vero cells using directly the tear film HSV populations allowed the prediction of the resistance by an early rise in the effective dose 90% (ED 90) value anticipating that in ED 50%. An ED 50 determination by dye-uptake assay on P6 HSV isolate demonstrated a cross resistance to viral thymidine kinase (TK) dependent drugs without any change in Ara-A and PFA sensitivity, according to a 23% TK activity at P6. At the last passage the HSV drug resistant population had an unrestricted corneal pathogenicity. A return to IDU and ACV in vitro sensitivity was demonstrated in group control animals at P2 but not at P4 or P6.
在兔体内进行6代连续传代（P1至P6）期间，研究了反复局部给予碘苷（IDU）对单纯疱疹病毒1型（HSV1）毒株敏感性的影响。与接受安慰剂治疗的兔子相比，在P2时溃疡愈合出现延迟，在P3时产生临床耐药性。在P7时还测试并证实了对阿昔洛韦（ACV）的临床交叉耐药性。在体外，直接使用泪膜HSV群体对Vero细胞进行蚀斑减少试验，通过有效剂量90%（ED 90）值的早期升高来预测耐药性，该值早于ED 50%时的升高。根据P6时23%的胸苷激酶（TK）活性，通过对P6 HSV分离株进行染料摄取试验测定ED 50，结果显示对病毒TK依赖性药物存在交叉耐药性，而对阿糖腺苷（Ara - A）和磷甲酸（PFA）的敏感性没有变化。在最后一代传代时，HSV耐药群体具有不受限制的角膜致病性。在P2时，对照组动物恢复了对IDU和ACV的体外敏感性，但在P4或P6时未恢复。
