中华流行病学杂志
中華流行病學雜誌
중화류행병학잡지
CHINESE JOURNAL OF EPIDEMIOLOGY
2011年
5期
499-503
,共5页
李韩平%郭伟%刘永健%鲍作义%李林%庄道民%刘思扬%王铮%王晓林%李敬云
李韓平%郭偉%劉永健%鮑作義%李林%莊道民%劉思颺%王錚%王曉林%李敬雲
리한평%곽위%류영건%포작의%리림%장도민%류사양%왕쟁%왕효림%리경운
HIV-1%B′亚型%新型耐药突变
HIV-1%B′亞型%新型耐藥突變
HIV-1%B′아형%신형내약돌변
HIV-1%Subtype B'%Novel resistance mutations
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HIV-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1977 bp.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-1 B′亚型病毒株7个突变可能与耐药有关.
目的 篩選HIV-1 B′亞型病毒株中可能存在的新型耐藥相關突變位點.方法 收集整理前期研究穫得的451條HIV-1B′亞型pol區基因序列,序列含蛋白酶全長(1～99箇密碼子)和反轉錄酶全長(1～560箇密碼子),長度約1977 bp.將354條來自接受抗病毒治療艾滋病患者的(服藥組)序列與97條來自未接受治療患者的(未服藥組)序列,分彆與B亞型野生型pol基因共享序列進行逐箇密碼子比對,篩選在服藥組序列中齣現的頻率顯著高于未服藥組序列的突變位點,將篩選齣來的突變位點在斯坦福大學HIV-1耐藥數據庫中檢索,根據數據庫收錄的情況及解釋,初步分析突變與耐藥的關繫.結果 在服藥組序列中反轉錄酶區有6箇位點7箇突變的頻率顯著高于未服藥組,分彆是D123E、V292I、K366R、T369A、T369V、A371V和1375V,即前2箇突變位于反轉錄酶的聚閤酶區、後5箇突變位于反轉錄酶的連接區.檢索數據庫收錄情況,有7箇突變均為相應位點的主要變異形式,在服藥患者中齣現的頻率顯著高于未服藥患者.結論 篩選齣的HIV-1 B′亞型病毒株7箇突變可能與耐藥有關.
목적 사선HIV-1 B′아형병독주중가능존재적신형내약상관돌변위점.방법 수집정리전기연구획득적451조HIV-1B′아형pol구기인서렬,서렬함단백매전장(1～99개밀마자)화반전록매전장(1～560개밀마자),장도약1977 bp.장354조래자접수항병독치료애자병환자적(복약조)서렬여97조래자미접수치료환자적(미복약조)서렬,분별여B아형야생형pol기인공향서렬진행축개밀마자비대,사선재복약조서렬중출현적빈솔현저고우미복약조서렬적돌변위점,장사선출래적돌변위점재사탄복대학HIV-1내약수거고중검색,근거수거고수록적정황급해석,초보분석돌변여내약적관계.결과 재복약조서렬중반전록매구유6개위점7개돌변적빈솔현저고우미복약조,분별시D123E、V292I、K366R、T369A、T369V、A371V화1375V,즉전2개돌변위우반전록매적취합매구、후5개돌변위우반전록매적련접구.검색수거고수록정황,유7개돌변균위상응위점적주요변이형식,재복약환자중출현적빈솔현저고우미복약환자.결론 사선출적HIV-1 B′아형병독주7개돌변가능여내약유관.
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(codous 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, DI23E, V292I, K366R, T369A, T369V, A371V and 1375V, 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 7mutations 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.
