中华传染病杂志
中華傳染病雜誌
중화전염병잡지
CHINESE JOURNAL OF INFECTIOUS DISEASES
2010年
8期
449-454
,共6页
苏齐鉴%闭志友%周平%肖信%岑平%邓伟%蓝光华%蒋俊俊%梁冰玉%刘伟%梁浩
囌齊鑒%閉誌友%週平%肖信%岑平%鄧偉%藍光華%蔣俊俊%樑冰玉%劉偉%樑浩
소제감%폐지우%주평%초신%잠평%산위%람광화%장준준%량빙옥%류위%량호
基因型%抗药性,病毒%突变%HIV-1%蛋白质亚型
基因型%抗藥性,病毒%突變%HIV-1%蛋白質亞型
기인형%항약성,병독%돌변%HIV-1%단백질아형
Genotype barrier%Drug resistance,viral%Mutation%HIV-1%Protein isoforms
目的 比较HIV-1 CRF01_AE、CRF07_BC和CRF08_BC毒株发生蛋白酶抑制剂(PI)、核苷类反转录酶抑制剂(NRTI)和非核苷类反转录酶抑制剂(NNRTI)主要耐药性突变的基因屏障,分析不同亚型耐药模式的差异.方法 纳入在广西壮族自治区南宁、柳州两市未经治疗的HIV感染者190例,采集外周静脉血,从血浆中提取HIV-1 RNA,扩增pol区并测序,用系统进化树分析序列的亚型,统计各序列每个主要突变位点由野生型密码子突变为耐药密码子所需的碱基转换和颠换的数量,根据转换与颠换发生概率约2.5:1的规律,将每个转换赋值设为1,每个颠换赋值设为2.5,计算各突变赋值之和,即为基因屏障值,采用Kruskal-Wallis检验法和Nemenyi法比较不同亚型的基因屏障差异.结果 共获得CRF01_AE、CRF07_BC和CRF08_BC毒株123株.CRF08_BC发生T/S69D的基因屏障低于CRF01_AE和CRF07_BC(χ2=107.501,P＜0.01),CRF01_AE和CRF07_BC发生V118I和L210W的基因屏障低于CRF08_BC,CRF07_BC发生V106M的基因屏障低于CRF01_AE和CRF08_BC.结论 在相同的选择压力下,CRF01_AE和CRF07_BC比CRF08_BC易发生V118I和L210W,CRF08_BC比CRF01_AE和CRF07_BC易发生T/S69D,CRF07_BC比CRF08_BC和CRF01_AE易发生V106M.
目的 比較HIV-1 CRF01_AE、CRF07_BC和CRF08_BC毒株髮生蛋白酶抑製劑(PI)、覈苷類反轉錄酶抑製劑(NRTI)和非覈苷類反轉錄酶抑製劑(NNRTI)主要耐藥性突變的基因屏障,分析不同亞型耐藥模式的差異.方法 納入在廣西壯族自治區南寧、柳州兩市未經治療的HIV感染者190例,採集外週靜脈血,從血漿中提取HIV-1 RNA,擴增pol區併測序,用繫統進化樹分析序列的亞型,統計各序列每箇主要突變位點由野生型密碼子突變為耐藥密碼子所需的堿基轉換和顛換的數量,根據轉換與顛換髮生概率約2.5:1的規律,將每箇轉換賦值設為1,每箇顛換賦值設為2.5,計算各突變賦值之和,即為基因屏障值,採用Kruskal-Wallis檢驗法和Nemenyi法比較不同亞型的基因屏障差異.結果 共穫得CRF01_AE、CRF07_BC和CRF08_BC毒株123株.CRF08_BC髮生T/S69D的基因屏障低于CRF01_AE和CRF07_BC(χ2=107.501,P＜0.01),CRF01_AE和CRF07_BC髮生V118I和L210W的基因屏障低于CRF08_BC,CRF07_BC髮生V106M的基因屏障低于CRF01_AE和CRF08_BC.結論 在相同的選擇壓力下,CRF01_AE和CRF07_BC比CRF08_BC易髮生V118I和L210W,CRF08_BC比CRF01_AE和CRF07_BC易髮生T/S69D,CRF07_BC比CRF08_BC和CRF01_AE易髮生V106M.
목적 비교HIV-1 CRF01_AE、CRF07_BC화CRF08_BC독주발생단백매억제제(PI)、핵감류반전록매억제제(NRTI)화비핵감류반전록매억제제(NNRTI)주요내약성돌변적기인병장,분석불동아형내약모식적차이.방법 납입재엄서장족자치구남저、류주량시미경치료적HIV감염자190례,채집외주정맥혈,종혈장중제취HIV-1 RNA,확증pol구병측서,용계통진화수분석서렬적아형,통계각서렬매개주요돌변위점유야생형밀마자돌변위내약밀마자소수적감기전환화전환적수량,근거전환여전환발생개솔약2.5:1적규률,장매개전환부치설위1,매개전환부치설위2.5,계산각돌변부치지화,즉위기인병장치,채용Kruskal-Wallis검험법화Nemenyi법비교불동아형적기인병장차이.결과 공획득CRF01_AE、CRF07_BC화CRF08_BC독주123주.CRF08_BC발생T/S69D적기인병장저우CRF01_AE화CRF07_BC(χ2=107.501,P＜0.01),CRF01_AE화CRF07_BC발생V118I화L210W적기인병장저우CRF08_BC,CRF07_BC발생V106M적기인병장저우CRF01_AE화CRF08_BC.결론 재상동적선택압력하,CRF01_AE화CRF07_BC비CRF08_BC역발생V118I화L210W,CRF08_BC비CRF01_AE화CRF07_BC역발생T/S69D,CRF07_BC비CRF08_BC화CRF01_AE역발생V106M.
Objective To compare the genetic barriers to development of primary mutations related to drug resistance to protease inhibitors (PI), nucleioside reverse transcriptase inhibitors ( NRTI ), and non-nucleioside reverse transcriptase inhibitors ( NNRTI ) among human immunodeficiency virus (HIV)-1 CRF01_AE, CRF07_BC, and CRF08_BC strains, and to understand the difference of varying patterns of drug resistance related mutations within these subtypes. Methods One hundred and ninety naive HIV-positive subjects from Nanning City and Liuzhou City, Guangxi Zhuang Autonomous Region, were recruited. Peripheral blood samples were collected from all participants. HIV-1 RNAs were extracted from plasma, and the pol regions were amplified and sequenced. Sequences were subjected to phylogenetic analysis to determine the subtypes of HIV-1 isolates. Nucleotide transitions and transversions were counted for each primary mutation in these sequences. According to the phenomena that transitions occur on average 2. 5 times frequently than transversions, each transition was scored as 1, and each transversion scored as 2. 5. The sum of the scores for a particular substitution was calculated, and this value was taken as the genetic barrier to development of this mutation. Then, the differences of genetic barriers among the subtypes were assessed by Kruskal-Wallis test and Nemenyi test. Results A total of 123 sequences of CRF01_AE,CRF07_BC and CRF08_BC strains were selected. CRF08_BC had a lower genetic barrier for T/S69Dsubstitution than CRF01_AE and CRF07_BC (χ2 =107. 501, P＜0.01), while CRF01_AE and CRF07_BC had lower genetic barriers for V118I and L210W substitution than CRF08_BC. In addition,CRF07_BC had a decreased genetic barrier for V106M compared with CRF01_AE and CRF08_BC.Conclusions In the presence of the same selective pressure, subtypes CRF01_AE and CRF07_BC may be more likely to develop V118I and L210W substitution than CRF08_BC. However, CRF08_BC may be more likely to develop T/S69D substitution than CRF01_AE and CRF07_BC. Meanwhile, CRF07_BC may be easier to develop V106M substitution than CRF01_AE and CRF08_BC.
