HIV-1基因亚型研究现状

艾滋病病毒(HIV)的典型遗传特征之一是高度的遗传变异性。根据其基因序列和氨基酸序列的特征,HIV可分为多种亚型。本文主要叙述HIV亚型的基因分型及检测、HIV-1 M组基因亚型的形成、HIV-1亚型与流行特征及与发病的关系等,有助于深入了解HIV的起源、流行规律和地理分布,对HIV的检测诊断、发病等方面有指导作用。     

HIV-1基因突变株对贵州省艾滋病流行的影响

目的研究HIV-1基因突变株对艾滋病流行的关系,为控制艾滋病流行提供科学依据。方法分3个时段检测贵州省多地区192份HIV-1毒株样本,用套式PCR扩增其Env、Gag基因和测序分析,实验结果与贵州省艾滋病流行现状进行相关分析。结果贵州省HIV-I毒株经变异产生了CRF07-BC、CRF08-BC、CRF01-AE3种新的基因重组亚型毒株,亚型的产生、传播与贵州省艾滋病的暴发流行高度相关。结论 HIV-1毒株的突变或重组是加速贵州省艾滋病传播与流行的因素之一;HIV-1基因突变引起亚型改变先于HIV的暴发流行,及时监控HIV-1基因突变,可作为防控艾滋病暴发流行的先行指标之一。     

流动人口对HI V-1流行特征影响的研究

目的：分析浙江省及与艾滋病疫情相关的9个省（自治区） HIV-1流行毒株亚型特征间的关系,了解流动人口对HIV-1流行特征的影响。方法检索并分析浙江省及与浙江省艾滋病疫情相关的9个省（自治区） HIV-1疫情、流行毒株构成及变迁的文献,查找两者毒株亚型间的联系。结果流动人口在HIV疫情流行地区与低流行地区间的传播中起着“桥梁”作用。流动人口输出较多的中西部省份HIV疫情相对高发,不同省HIV流行毒株有差异。目前,浙江省HIV-1型流行毒株以CRF01＿AE、CRF07＿BC、CRF08＿BC和B’亚型为主,4种亚型占97.78％。浙江省流行的亚型构成,与流动人口输出地的HIV流行亚型及其变迁有关。结论 HIV疫情高发省份的外来流动病例对浙江省HIV疫情的传播和流行会造成一定影响,需继续加强HIV毒株监测。     

宁夏HIV-1感染者原发性耐药及基因变异型研究

目的 掌握本地区HIV-1 病毒耐药毒株的流行与传播情况,为有效的抗病毒治疗提供参考依据。方法 2018年3月1日-6月30日在宁夏开展HIV/AIDS抗病毒治疗前HIV-1耐药的横断面调查。提取获得HIV-1 pol基因区序列,根据2015年WHO耐药监测指南的推荐标准,采用Shafer 的耐药性突变积分表耐药评分,分值≥15判为耐药。结果 调查68例HIV/AIDS,58例巢式PCR检测获得HIV-1病毒pol区基因序列。年龄中位数为36.5岁（IQR:30～50）;男性55例(94.8%),女性3例(5.2%), Shafer 的耐药性突变积分表耐药评分,7例判为耐药,耐药率12.1%。存在4种基因亚型,分别是B亚型、CRF01_AE 亚型、CRF07_BC亚型和CRF55_01B亚型。结论 宁夏HIV-1原发性耐药率处于较高水平,应继续加强艾滋病抗病毒治疗前耐药监测。     

昆明市2010年HIV-1耐药传播警戒线调查

目的 了解2010年昆明市未经抗病毒治疗的HIV感染者中耐药株的传播水平.方法 根据WHO推荐的HIV耐药警戒线调查方法,对2010年1-8月收集的62份年龄＜25岁的HIV-1新发现感染者的血液样本进行HIV-1耐药基因型检测和耐药株传播水平分析.结果 62份样本中,54份完成耐药基因型鉴定.按pol基因区进行分型,其中53.2％的样本为CRF08 BC亚型,其他亚型包括CRF07_BC、CRF01_AE、C.根据采样时间顺序,前47份扩增阳性的样本用于耐药传播水平的分析,其中1份出现针对蛋白酶抑制剂类药物的耐药突变位点,耐药株流行率＜5％.结论 昆明市HIV耐药株尚处于低度流行水平,为控制耐药传播水平的上升,规范治疗及科学管理仍然是当前艾滋病患者治疗工作的重点.     

HIV亚型特性及其意义

根据基因序列和氨基酸序列的特征,艾滋病病毒(HIV)可分为诸多的亚型。HIV亚型的研究有助于人们更深入了解HIV的起源、流行规律和地理分布,对HIV的临床诊断、药物治疗、疫苗研制及控制对策等方面具有重要的指导作用。     

深圳口岸出入境人员HIV感染情况及其分子特征

目的为了揭示深圳口岸出入境人员艾滋病病毒(HIV)感染者的流行病学特征以及HIV亚型的分布情况。方法以1991—2008年深圳国际旅行卫生保健中心HIV确证实验室检测的113例HIV感染者为研究对象,分析了深圳口岸出入境人员艾滋病的流行特征;并对HIV感染者的HIV-1抗体阳性血浆进行HIV基因型分析。结果 HIV感染者以境外人员为主,男性高于女性,感染人员以商人和驾驶员为主,感染群体以青壮年为主,两性接触是主要传播途径,感染者来自26个国家和地区。本研究共获得67份gag基因和68份pol基因序列,共发现9种HIV-1亚型和重组亚型,包括A1、B、C、D和G亚型以及CRF01_AE、CRF02_AG、CRF07_BC和CRF08_BC重组亚型。结论深圳口岸出入境人员HIV的感染和流行呈多样化,我国国境卫生检疫在防控艾滋病传播中已发挥了重要作用。     

HIV亚型特性及其意义

根据基因序列和氨基酸序列的特征，艾滋病病毒(HIV)可分为诸多的亚型。HIV亚型的研究有助于人们更深入了解HIV的起源、流行规律和地理分布，对HIV的临床诊断、药物治疗、疫苗研制及控制对策等方面具有重要的指导作用。     

2008年安徽省原发HIV-1感染者耐药毒株变异情况研究

目的分析安徽省艾滋病病毒1型(human immunodeficiency virus 1,HIV-1)在原发感染人群中耐药毒株变异情况,为全省艾滋病抗病毒及耐药性监测方案的制定提供科学依据。方法参照世界卫生组织提出的HIV耐药警戒线调查方法(HIV drug resistance threshold survey,HIVDR-TS)指导方案,采用横断面调查,收集安徽省2008年度检测的58名小于25岁的HIV-1感染者血浆样本,进行HIV-1 POL区亚型及耐药基因型分析。结果获得49份样本,POL区29个有效序列中,B/C重组亚型比例最大,达44.8%,其次为B亚型,占37.9%。没有针对PR区的主要耐药性基因突变,PR区耐药株流行率为0。29个序列中针对核苷酸反转录酶区(NRTI)的耐药突变有2例,非核苷酸反转录酶区(NNRTI)有4例,仅V179D突变对依非韦仑(EFV)和奈韦拉平(NVP)出现潜在耐药,RT区耐药株流行率为3.4%,均属于低度流行(<5%)。结论安徽省未经抗病毒治疗新发HIV-1感染者中已经出现POL区耐药突变株,但传播水平尚处于低流行状态,治疗前尚不需要进行大规模耐药性监测。     

2008年安徽省原发HIV-1感染者耐药毒株变异情况研究

目的分析安徽省艾滋病病毒1型（human immunodeficiency virus 1,HIV-1）在原发感染人群中耐药毒株变异情况,为全省艾滋病抗病毒及耐药性监测方案的制定提供科学依据。方法参照世界卫生组织提出的HIV耐药警戒线调查方法（HIV drug resistance threshold survey,HIVDR-TS）指导方案,采用横断面调查,收集安徽省2008年度检测的58名小于25岁的HIV-1感染者血浆样本,进行HIV-1 POL区亚型及耐药基因型分析。结果获得49份样本,POL区29个有效序列中,B/C重组亚型比例最大,达44.8%,其次为B亚型,占37.9%。没有针对PR区的主要耐药性基因突变,PR区耐药株流行率为0。29个序列中针对核苷酸反转录酶区（NRTI）的耐药突变有2例,非核苷酸反转录酶区（NNRTI）有4例,仅V179D突变对依非韦仑（EFV）和奈韦拉平（NVP）出现潜在耐药,RT区耐药株流行率为3.4%,均属于低度流行（<5%）。结论安徽省未经抗病毒治疗新发HIV-1感染者中已经出现POL区耐药突变株,但传播水平尚处于低流行状态,治疗前尚不需...     

Demographic history of HIV-1 subtypes B and F in Brazil.

The reconstruction of the epidemic history of several HIV populations, by using methods that infer the population history from sampled gene sequence data, has revealed important subtype-specific and regional-specific differences in patterns of epidemic growth. Here, we employ Bayesian coalescent-based methods to compare the population history of the HIV-1 subtype B and F1 epidemics in Brazil from non-contemporary env and pol gene sequences. Our results suggest that after the introduction of the subtypes B and F1 into Brazilian population, around mid to late 1960s and late 1970s, respectively, these subtypes experienced an initial period of exponential growth with similar epidemic growth rates ( approximately 0.5-0.6year(-1)). Later, the spreading rate of both subtypes seems to have slowed-down since mid to late 1980s. This demographic pattern is very similar to that reported for the subtype B epidemics in high-income countries where HIV was initially transmitted through homosexual intercourse and injecting drug use, as in Brazil; suggesting that the characteristics of transmission networks may be a key determinant of the HIV epidemic growth pattern. It is important to note that most of the subtype B and F1 sequences used in this study come from the Southeast region that has been the most affected by the AIDS epidemic in Brazil, being responsible for around 63% of all AIDS cases reported since the early eighties; but may not represent the demographic trend of the HIV-1 epidemic in other Brazilian regions.     

Analysis of the near full length genomes of HIV-1 subtypes B, F and BF recombinant from a cohort of 14 patients in S?o Paulo, Brazil.

The human immune deficiency virus (HIV) exhibits strikingly tremendous amount of genetic variability. Such feature is critically important for the virus to adapt to environmental changes by escaping the host immune system and by escaping candidate vaccine. Therefore, understanding of such diversity is fundamental for the design of successful drugs or vaccine, which is urgently needed to bring the HIV/AIDS epidemic under control. In this study, we investigated the magnitude of diversity of the HIV-1 near full-length genomes from patients previously assigned as infected with non-recombinant HIV-1 subtypes B and F1 variants based on small portion of viral genome. HIV-1 proviral DNA was extracted from 14 samples previously classified in our laboratory as six subtypes B and eight subtypes F on the basis of small amplicon sequencing. Reamplifications of DNA from these samples were carried out by an overlapping PCR followed by direct sequencing. The data were phylogenetically inferred. Sequence analysis revealed that two out of six partially identified subtype B and six out of eight partially identified subtype F were in fact BF recombinants throughout their full genomes. Two pairs BF recombinants had identical genomic recombination structure and distinct from the Argentinean CRF 12_BF strains, probably represents a novel circulating recombinant forms in Brazil. Our data provided new genetic material of some of the HIV-1 subtypes currently circulating in the country and points to the widespread of BF recombinants which are expected to change the epidemic nature by approaching the level of subtype B in Brazil.     

Construction and in vitro characterization of a molecularly cloned human immunodeficiency virus type 1 library.

Development of a safe and effective vaccine against human immunodeficiency virus (HIV) is urgent, but many concerns regarding the safety and efficacy of the currently developing vaccines remain. A major hindrance in HIV vaccine development is the genetic diversity, a hallmark of HIV biology, and a poor understanding of how HIV vaccine prevents the emergence of escape variants during infection and progression of AIDS. Here, we developed a method to construct a molecularly cloned viral library. This technique employs a long-range polymerase chain reaction (PCR) to amplify a virtually full-length HIV type 1 (HIV-1) provirus genome from peripheral blood mononuclear cells (PBMCs) infected with CRF01_AE (subtype E) Thai primary isolate. Among randomly selected 93 clones, 41 with a full-length sequence were able to replicate in PBMCs, 5 of which induced strong cytopathic effects. Replication kinetics also showed that the parental virus was intermediate among the clones. Thus, the molecular library prepared by this method showed the quasi-species in infected cells and this method could provide a new possibility for the development of an order-made therapeutic vaccine against HIV-1.     

HIV/AIDS患者基因变异与疾病关系的研究

目的 研究HIV-1感染者／AIDS患者体内不同亚型HIV-1tat基因序列特征、突变特点及与疾病进展的关系。方法 采集辽宁省22例HIV感染者／AIDS患者的血液样本，提取含有整合HIV-1前病毒的基因组DNA，nested-PCR扩增后直接测序，并做序列排列比对、翻译和分析。结果22株辽宁省流行的HIV-1病毒分属B^ 及B^ ／C重组亚型。AIDS患者体内病毒tat区第一显子发生氨基酸突变，58位点出现T取代A，无症状感染者未发现此变异。此外还发现7，20，24,59，62，64位点出现取代变异，这些变异在AIDS病组要高于无症状感染组。结论 B^ 和B^ ／C重组亚型HIV-1tat基因第一外显子氨基酸序列发生的变异与疾病进展相关；同时还发现AIDS患者的tat基因第一外显子的其它一些取代变异。     

福建省艾滋病感染的流行病学和病毒亚型 之间相互关系的研究

目的通过分子流行病学调查,明确福建省人类免疫缺陷病毒-1(HIV-1)流行毒株亚型与艾滋病(AIDS)流行的关系.方法通过艾滋病监测网络发现全省HIV/AIDS病例,应用核苷酸序列分析技术确定HIV-1亚型,结合流行病学资料分析福建省AIDS的流行状况.结果截至2000年底,全省累计发现188例HIV感染者,其中AIDS59例(已死亡53例).经异性性接触感染占65.4%,经血途径感染占9.0%,境外感染占44.1%,其中在东南亚等国家感染约占83.1%,境内感染占39.9%.41例HIV/AIDS病例的HIV-1亚型分析表明福建省存在A、B、C和E4种亚型,E亚型占75.6%(31/41),均为经异性性接触途径感染;B亚型17.1%(7/41),主要经血途径感染.A和C亚型分别为1和2例.E亚型基因离散率为(12.245±3.894)%,B亚型基因离散率为(10.762±2.707)%.表明福建省E亚型流行株的来源复杂,与感染地点、时间有关.结论福建省AIDS流行速度正在加快,病毒感染者主要经异性性接触途径感染,HIV-1流行毒株主要为E亚型.     

辽宁省HIV-1株的基因序列测定和亚型分析

目的　通过DNA序列分析 ,确定辽宁省HIV -1流行毒株的亚型。方法　从辽宁省HIV -1抗体阳性者中选择 16例 ,其中经性接触感染者 8例 ,经静脉吸毒和血液途径感染者 7例 ,垂直传播者 1例 ,采集全血提取DNA作为PCR扩增的模板 ,套式引物扩增HIV -1前病毒DNA的C2～V 3区用于测序。所测序列与国际标准株及国内外参考序列进行比较 ,确定被检标本的亚型。结果　辽宁省流行的HIV -1病毒分属A、B、C、G4种亚型 ,其中经性途径传播者 8例分别为B′亚型和A亚型 ,静脉吸毒者 4皆为C亚型 ,经血途径感染者分别属B′和G亚型 ,垂直传播者为A亚型。亚型内基因离散率分别为 :A亚型 (7 5± 1 0 ) % ,B′亚型 (8 5± 0 9) % ,C亚型 (5 4± 0 9) % ,G亚型 (13 5±2 1) %。结论　辽宁省目前HIV -1的流行株亚型较为复杂 ,不同传播途径感染HIV毒株亚型有所不同 ,C亚型毒株只见于静脉吸毒者 ,经性途径和血途径感染主要为B′亚型 ,而A亚型和G亚型只见于非洲劳务输出人员及其配偶子女。     

Progress towards an HIV-1 subtype C vaccine

Several scientific fields related to vaccine development have made significant advances in understanding how to design immunogens against selected infectious pathogens. In the case of human immunodeficiency virus type-1 (HIV-1), anti-retroviral (ARV) drugs have dramatically improved the health and extended the lives of people with HIV/AIDS. However, their high cost of implementation and demanding clinical requirements put them out of reach of the vast majority of people with HIV, especially in developing countries where HIV infection levels are high and public resources are extremely scarce. With 25.4 million people living with HIV/AIDS in sub-Saharan Africa as of the end of 2004 (http://www.unaids.org), this region was still by far the worst-affected in the world with HIV-1 subtype C (HIV-1C) accounting for the majority of infections. Although the constraints placed by HIV genetic variation on vaccine efficacy remain unclear, there is an indication that they may be important and several candidate vaccines targeting HIV-1C are currently under investigation in both pre-clinical and clinical settings. The designs of these candidate HIV-1C vaccines focus on both regulatory and structural HIV-1 proteins derived from HIV-1C. They make use of a number of current vaccine technologies for their delivery to invoke adaptive immune responses in individuals that hopefully may prove to be protective. This review looks at the progress and accomplishments made thus far in the generation and testing of such HIV-1C vaccines.     

广东省艾滋病患者HIV-1基因亚型分析

目的 了解目前广东省HIV/AIDS患者HIV-1基因型的流行状况.方法 用套式PCR对222例HIV/AIDS患者外周血单核细胞(PBMC)中HIV前病毒DNA膜蛋白env基因C2-V4区及其邻近区域片段进行扩增,并对片段进行序列测定,与国际HIV-1标准毒株序列进行比较,依据同源性确定基因型.结果 222例患者中,...     

江苏省艾滋病病毒感染的分子流行病学研究

目的 了解江苏省不同人群中艾滋病病毒(HIV)各亚型毒株的流行情况和传播规律。方法 收集HIV感染者及患者的流行病学资料；无菌采集HIV感染者或艾滋病(AIDS)患者抗凝全血标本5ml，提取前病毒DNA，用巢式聚合酶链反应(nested—PCR)扩增膜蛋白基因的C2～V3区，进行序列测定，鉴定病毒亚型。用威斯康星GCG软件进行共享序列、基因离散率的计算和毒株的聚类分析。结果 截止2001年底，江苏省已发现HIV-1中的A、B、C、D、E五种亚型和一个B亚型变种(B^ )流行，C(占40．48％)和B^ (38．10％)亚型为主要流行株；静脉吸毒感染人群中86．67％为C亚型，采供血和受血感染人群中91．67％为B^ 亚型，在性途径传播人群中所有六种亚型均有，且分布较为均一。结论有偿献血人群中B^ 亚型毒株由邻省传人，吸毒人群中C亚型毒株的传人主要与新疆籍流动人口的介入有关；多种亚型的并存说明江苏省存在着适宜AIDS流行的各种危险因素；提示今后在药物治疗、疫苗研制以及其他防制工作上将面临更大的困难。