CAJ | 학술논문

目的探讨HIV-1的CRF_07BC重组型在药物压力下的进化通路,并与B亚型进行比较.方法病毒样本来自2007-2011年新疆维吾尔自治区和四川省参加艾滋病多中心队列研究的共862例AIDS患者.根据未治疗的588例和治疗的274例AIDS患者病毒样本的逆转录酶区序列,采用选择压力的方法识别耐药相关位点,使用贝叶斯网络法构建CRF 07BC重组型在抗病毒治疗下的耐药进化通路,同时利用国际HIV耐药数据库中的数据构建B亚型在相同治疗方案下耐药进化通路,并与CRF_07BC重组型进行比较.结果预测的CRF_07BC重组型主要耐药位点为K103N、Q197K、V179D和Y188L.预测的B亚型主要耐药位点为M184V、K103N、Y181C、T69N、G190A、K238T、Y188H和P225H.两者重叠较小,但经典的TAM1(41L、210W和215Y)和TAM2(67N、70R和219E/Q)通路均存在于两个病毒类型中.不同于B亚型的是,预测的CRF_07BC重组型的主要耐药位点中不包含TAM相关突变,并且在核苷类药物相关突变与非核苷类药物相关突变之间存在强的依赖关系.结论 HIV-1 CRF_07BC重组型形成了以K103N、Q197K、V179D和Y188L为主要耐药位点的独特耐药进化通路,并与B亚型的耐药进化通路有较大差异.
목적 탐토HIV-1적CRF_07BC중조형재약물압력하적진화통로,병여B아형진행비교.방법 병독양본래자2007-2011년신강유오이자치구화사천성삼가애자병다중심대렬연구적공862례AIDS환자.근거미치료적588례화치료적274례AIDS환자병독양본적역전록매구서렬,채용선택압력적방법식별내약상관위점,사용패협사망락법구건CRF 07BC중조형재항병독치료하적내약진화통로,동시이용국제HIV내약수거고중적수거구건B아형재상동치료방안하내약진화통로,병여CRF_07BC중조형진행비교.결과 예측적CRF_07BC중조형주요내약위점위K103N、Q197K、V179D화Y188L.예측적B아형주요내약위점위M184V、K103N、Y181C、T69N、G190A、K238T、Y188H화P225H.량자중첩교소,단경전적TAM1(41L、210W화215Y)화TAM2(67N、70R화219E/Q)통로균존재우량개병독류형중.불동우B아형적시,예측적CRF_07BC중조형적주요내약위점중불포함TAM상관돌변,병차재핵감류약물상관돌변여비핵감류약물상관돌변지간존재강적의뢰관계.결론 HIV-1 CRF_07BC중조형형성료이K103N、Q197K、V179D화Y188L위주요내약위점적독특내약진화통로,병여B아형적내약진화통로유교대차이.
Objective To study resistance evolution pathway of HIV-1 CRF_ BC under drug selection pressure,and compare with B subtype.Methods Based on the reverse transcriptase region of CRF_97BC HIV-1 from 588 treatment-naive and 274 treatment patients,selection pressure based method was used to select resistance-associated mutations,and Bayesian network was used to construct the resistance evolutionary pathway under antiretroviral therapy.Meanwhile,it was constructed that the resistance evolutionary pathway for B subtype with the same regimens using the data from HIV resistance database,and made a comparison with CRF_07BC.Results The major resistance mutations for CRF_07BC were identified including K103N,Q197K,V179D and Y188L.While for B subtype,the major resistance mutations include M184V,K103N,Y181C,T69N,G190A,K238T,Y188H and P225H.Much difference was observed between these two classes.However,the classical TMA1 (41L,210W and 215Y) and TMA2 (67N,70R and 219E/Q)pathways exist in both pathways.As different from B subtype,the predicted major drug resistance mutations for CRF _07BC did not contain TAM-related mutations,and nucleoside reverse transcriptase inhibitor-related mutations and non-nucleoside reverse transcriptase inhibitor-related mutations were mutually depending on each other.Conclusion HIV-1 CRF_07BC showed distinctive resistance evolutionary pathway,the mutations K103N,Q197K,V179D and Y188L were the major resistance mutations,and different resistance evolutionary pathways were observed between HIV-1 CRF_07BC and B subtype.