HSV对Carbocyclic Oxetanocin G的耐药性及耐药病毒的胸腺嘧啶核苷激酶的活性研究  

Resistance of HSV-1 to Carbocyclic Oxetanocin G and its relevance to Thymidine kinase activity

作　　者：胡楠[1] 龚启荣[1] 

机构地区：[1]江苏省南通医学院附属医院眼科,226001

出　　处：《眼科研究》2005年第5期498-500,共3页Chinese Ophthalmic Research

基　　金：江苏省科委社会发展基金资助(BS200070)

摘　　要：目的探讨治疗疱疹病毒性角膜炎的新药CarbocyclicoxetanocinG(C.OXTG)耐药性的产生情况及产生耐药性的机制。方法将1型单纯疱疹病毒(HSV1)接种于非洲绿猴肾细胞,在含10μmol/LC.OXTG的环境中连续培养20代,通过空斑抑制试验测定各代病毒株对C.OXTG的敏感性,测定野生HSV1、培养20代后的HSV1的耐药性及其生物克隆株的胸腺嘧啶核苷激酶的活性。结果HSV1在含C.OXTG的环境中连续传代培养4代后,便出现了耐药性。培养20代后的病毒株及其克隆株的ED50为野生株的10倍,且病毒的TK酶活性远远低于野生病毒株。结论HSV1在含C.OXTG的环境中很快产生耐药性且耐药病毒株缺乏TK酶活性。Objective To elucidate the potentiality resistance of herpes simplex virus type 1 （ HSV-1 ） to carbocyclic oxetanocin G （ C. OXT-G） ,a new and effective antiviral drug,and its mechanism. Methods A laboratory strain of HSV-1 （ PH strain） was serially propagated in African green monkey kidney cells （ VERO cells） in the presence of 10 p.mol/L of C. OXT-G for 20 passages. The sensitivity of each generation of HSV-1 to C. OXT-G was determined by plaque-reduction assay. The thymidine kinase （TK） activity of wild HSV-1 （ the C. OXT-G resistant strain,passage 20） and its clones were measured. Results The ED50 of C. OXT-G to virus was increased from 1.85 × 10^-7 mol /L to 1.51 × 10^-6 mol/L in the 4th passage of HSV-1 after cuhured with 10 μmol /L of C. OXT-G,showing the emergence of resistant virus. At the end of the 20th passage,the ED50 of the resistant HSV-1 strain and its clones were lO-fold higher than that of the wild strain. The TK activity of the wild HSV-1 was gradually increased over time,and that of virus of C. OXT-G resistant strain from passage 20 and cloned stain was significantly inhibited and was lower than that of the wild strain. Conclusion The resistance of HSV-1 to C. OXT-G may appear after HSV-1 growing in the presence of the drug,and the deficiency of viral TK activity may be the key factor of the vires resistance to C. OXT-G.

关 键 词：Carbocyclic Oxetanocin G 耐药性 单纯疱疹病毒 胸腺嘧啶核侍激酶 

分 类 号：R446.5[医药卫生—诊断学]