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南宁市HIV-1/AIDS人群治疗前pol区遗传特性及蛋白结构分析

Study on pol Genetic Characteristics and Protein Structure of HIV-1/AIDS before Antiretroviral Treatment Patients in Nanning
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摘要 为探讨南宁市某县艾滋病病毒1型(HIV-1)感染人群中治疗前pol区遗传特性及蛋白结构变化情况,本研究通过RT-PCR扩增pol区部分序列并进行测序,将序列同源比对构建系统进化树;分型确定毒株亚型和斯坦福大学HIV耐药性数据库比对,分析耐药相关位点;SWISS-MODEL蛋白质同源数据库进行建模分析氨基酸的突变对蛋白质结构和功能的影响。本研究在90份HIV-1标本中获得46个pol区有效序列,共发现4种亚型,其中CRF01_AE占76.08%(35/46)、CRF08_BC占15.22%(7/46)、CRF07_BC占(3/46)6.52%、CRF59_01B1占2.17%(1/46);46个序列中有4例(8.69%)出现耐药突变位点,没有针对核苷酸反转录酶抑制剂(NRTI)的耐药突变;针对蛋白酶类抑制剂(PIs)1例,PR蛋白酶的柔性部位I47V位点发生突变,β折叠结构的I84V位点发生突变,都是异亮氨酸突变为缬氨酸;针对非核苷酸反转录酶抑制剂(NNRTI)有3例,2例位于活性中心的Y181C位点由酪氨酸突变为半胱氨酸,1例位于转角处的E138G位点由谷氨酸突变为甘氨酸。研究表明,南宁市某县HIV-1病毒CRF01_AE重组亚型比例最大,未经抗病毒治疗HIV1感染者中已经出现pol区耐药突变株,突变位点主要位于活性中心及柔性部位,传播水平已经处于中等流行状态。深入分析蛋白质与抑制剂相互作用机制,有助于为艾滋病抗病毒及耐药性监测方案提供科学依据。 To analyze the genetic characteristics and protein structure of HIV strains'pol gene and to obtain the background information of HIV drug resistance before antiretroviral treatment of HIV infected people in a county of Nanning,the pol region was amplified by RT-PCR and constructed the phylogenetic tree by Mega 5.1.The HIV-1 subtype and drug resistance was detected by bioinformatics website.The SWISS-MODEL protein homology database was used to model the effects of amino acid mutations on protein structure and function.Totally 46 HIV-1 pol sequences were obtained.The most common subtypes identified were CRF01_AE(76.08%),CRF08_BC(15.22%),CRF07_BC(6.52%),CRF59_01 B1(2.17%);Overall,the prevalence of transmitted drug resistance(TDR)was 8.69%(4/46).For 1 case of protease inhibitors(PIs),the I47 V site of the flexible site of PR protease was mutated,and the I84 V site of theβ-sheet structure was mutated,all of which were isoleucine to valine;3 cases for non-nucleotide reverse transcriptase inhibitors(NNRTI),2 cases of Y181 C located in the active center were mutated from tyrosine to cysteine,and 1 case of E138G located at the corner was mutated from glutamic acid to glycine.These studies showed that the proportion of CRF01_AE subtypes in a county of Nanning is the largest.The pol-resistant mutants have been found in HIV-1 infected patients without antiviral therapy.The mutation sites are mainly located in the active center and flexible sites,and the transmission level is already at moderate epidemic state.Analyzing the protein-inhibitor interaction mechanisms might provide a scientific basis for HIV anti-virus and drug resistance surveillance programs.
作者 裴建新 唐驰 秦剑秋 潘海西 栾苑 周吉 Pei Jianxin;Tang Chi;Qin Jianqiu;Pan Haixi;Luan Yuan;Zhou Ji(Nanning Center for Disease Control and Prevention,Nanning,530023)
出处 《基因组学与应用生物学》 CAS CSCD 北大核心 2019年第7期3368-3375,共8页 Genomics and Applied Biology
基金 国家自然科学基金(No.21366007) 广西壮族自治区卫生厅自筹经费课题(No.Z2012651 No.Z20170723)共同资助
关键词 人类免疫缺陷病毒1型 亚型 耐药性突变 同源建模 蛋白结构 HIV-1 Substyle Drug-resistant mutation Homology modeling Protein structure
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