HIV-1B′亚型毒株新型耐药相关突变位点的筛选  

Screening program on novel drug resistance mutations of subtype B′ in human immunodeficiency virus type 1 in China

作　　者：李韩平[1] 郭伟[1] 刘永健[1] 鲍作义[1] 李林[1] 庄道民[1] 刘思扬[1] 王铮[1] 王晓林[1] 李敬云[1] 

机构地区：[1]军事医学科学院微生物流行病研究所病原微生物生物安全国家重点实验室,北京100071

出　　处：《中华流行病学杂志》2011年第5期499-503,共5页Chinese Journal of Epidemiology

基　　金：国家自然科学基金（30830088,30800938）;“十一五”国家科技重大专项（2008ZX10001-004,2008ZX10001-013）

摘　　要：目的筛选HIV—1 B′亚型病毒株中可能存在的新型耐药相关突变位点。方法收集整理前期研究获得的451条H1V-1B′亚型pol区基因序列，序列含蛋白酶全长（1～99个密码子）和反转录酶全长（1～560个密码子），长度约1977bp。将354条来自接受抗病毒治疗艾滋病患者的（服药组）序列与97条来自未接受治疗患者的（未服药组）序列，分别与B亚型野生型pol基因共享序列进行逐个密码子比对，筛选在服药组序列中出现的频率显著高于未服药组序列的突变位点，将筛选出来的突变位点在斯坦福大学HIV-1耐药数据库中检索，根据数据库收录的情况及解释，初步分析突变与耐药的关系。结果在服药组序列中反转录酶区有6个位点7个突变的频率显著高于未服药组，分别是D123E、V292I、K366R、T369A、T369V、A371V和1375V，即前2个突变位于反转录酶的聚合酶区、后5个突变位于反转录酶的连接区。检索数据库收录情况，有7个突变均为相应位点的主要变异形式，在服药患者中出现的频率显著高于未服药患者。结论筛选出的HIV-1B′亚型病毒株7个突变可能与耐药有关。Objective To screen the level of novel drug resistance mutations in subtype B′ in China. Methods 451 pol sequences collected from the previous study, which including 354 AIDS patients who had received antiretroviral treatment（ART） and 97 the untreated patients. Entire protease gene （codons 1-99） and full-length reverse transcriptase gene （codons 1-560） were included. Variation of mutations between the treated and the untreated patients with consensus/ancestral sequences were compared and the mutations with higher frequencies in the treated patients than in the untreated patients were screened before submitting the mutations to the Stanford HIV Drug Resistance Database （SHDB）（http：//hivdb.stanford.edu/）. Relation between the mutations and resistance preliminarily was then analyzed, according to the information including SHDB. Results Frequencies of 7 mutations at 6 positions, D123E, V292I, K366R, T369A, T369V, A371V and I375V, 2 at DNA polymerase domain and 5 at connection domain of reverse transcriptase （RT） were higher in the treated patients than in the untreated patients. The information of 7 mutations including the SHDB showed that 7 mutations were major variants at corresponding positions, and theirs frequencies were higher in the treated patients using some drugs, than in the untreated patients. Conclusion 7 mutations being screened from the China subtype B were possibly associated with the resistance, which called for the construction of mutated viruses by site-directed mutagenesis to identify their effects on the susceptivity of different drugs.

关 键 词：HIV-1 B′亚型 新型耐药突变 

分 类 号：R373[医药卫生—病原生物学]