乙型肝炎病毒核苷类似物交叉耐药株RT区变异分析  

Analysis on variations of reverse transcriptase region in hepatitis B virus nucleoside analogues cross-resistant strains

作　　者：滕旭[1] 林乐勋[1] 陈丽玲[2] 梁爽[3] 徐晖[4] 谷鸿喜[1] 

机构地区：[1]哈尔滨医科大学微生物学教研室,黑龙江哈尔滨150081 [2]哈尔滨医科大学大庆校区检验系,黑龙江大庆163000 [3]哈尔滨市疾病预防控制中心,黑龙江哈尔滨150056 [4]哈尔滨医科大学医学遗传学教研室,黑龙江哈尔滨150081

出　　处：《国际检验医学杂志》2015年第9期1179-1181,共3页International Journal of Laboratory Medicine

基　　金：黑龙江省教育厅科学技术研究项目(12511179)

摘　　要：目的研究多种核苷类似物(NAs)序贯治疗产生交叉耐药的患者体内乙型肝炎病毒(HBV)RT区变异位点和变异类型。方法筛选6例临床上对两种或两种以上NAs产生交叉耐药的患者,并从患者血清中获取HBV交叉耐药株DNA,进行全基因克隆和测序,从而分析其变异特点和规律。结果经测序鉴定,6位患者体内HBV基因型均为C型,产生交叉耐药的相关性变异以rtM204V/I(YMDD)变异为主(50%),部分YMDD变异株伴有rtL180M变异(16.7%)、其他伴随变异包括rtV173L(16.7%),rtL80I(16.7%)。此外,还发现RT区次要变异伴随位点rtL269I(40%)、rtQ333K(56.7%)、rtH337N(56.7%)。结论RT区次要变异伴随位点rtL269I、rtQ333K、rtH337N的出现可能增强了HBV YMDD变异株在体内的复制能力,并对交叉耐药准种所占比例起到了放大的效果,从而导致本研究中6例患者出现对拉米夫定、恩替卡韦、阿德福韦和替比夫定产生多重耐药。Objective To study the sites and types of hepatitis B virus （HBV） variations at reverse transcriptase（RT） region in the patients with cross drug resistance generated by the nucleoside analogues （NAs） sequential treatment. Methods 6 adult pa tients with cross-resistance to 2 or above NAs were screened out. The DNA of cross resistant HBV strains was obtained from the serum of the patients and performed the whole-genome clone and sequencing for analyzing its variation characteristics and rule. Results The sequencing identification showed that HBV genotype in 6 patients was the type C and the related variations generating the cross drug resistance were dominated by rtM204V/I（ 50 % ）, rtL180M（ 16.7 % ）, rtV173I.（n = 16.7 % ） and rtL80I（n = 16.7 % ）. In addition,some secondary variations accompanying sites at the RT region such as rtL269I（40 % ）, rtQ333K（56.7%）, rtH337N （56.7%） were found. Conclusion The secondary variations at RT region could enhance the replication capacity of HBV YMDD variant strains,and enlarge HBV quasispecies variant populations, which caused the emergence of multi drug resistant mutant virus during sequential or combination therapy with lamivudine,entecavir,adefovir and telbivudine in 6 patients of this study.

关 键 词：乙型肝炎病毒 交叉耐药 病毒变异 

分 类 号：R373.21[医药卫生—病原生物学]