中国南方畲族人群中艾滋病感染相关等位基因基质细胞衍生因子1的频率和多态性分布

背景：基质细胞衍生因子是嗜淋巴细胞人类免疫缺陷病毒1感染的体外潜在抑制因子，可阻断人类免疫缺陷病毒1侵入人体的通路。目的：了解人类免疫缺陷病毒1感染相关等位基因基质细胞衍生因子-3’A在我国南方畲族人群中的频率和多态性分布，探讨畲族人未感染人类免疫缺陷病毒1的基因水平的可能原因。设计：单一样本研究。单位：赣南医学院生化与分子生物学教研室。对象：于1995-01/12从畲族主要居住地江西省铅山县、福建省宁德地区和浙江省景宁畲族自治县随机选择3代均为畲族的186名无人类免疫缺陷病毒1感染的无关个体作为观察对象。方法：随机采集血样186份，提取基因组DNA。经PCR-RFLP分析，计算基因突变频率；并对群体分布和性别分布进行统计分析。主要观察指标：中国畲族人群基质细胞衍生因子1基因型构成。结果：186人的数据均进入结果分析，无脱落者。基质细胞衍生因子-3’A频率为19．6％，群体分布符合Hardy-Weinberg平衡，性别之问无差异。结论：南方畲族人的基质细胞衍生因子-3＇A基因突变可能延缓艾滋病的发病进程，这一发现对于我国南方畲族人的艾滋病防治具有积极意义。     

上饶市无偿献血者抗-HIV-1阳性2例分析

艾滋病是由人类免疫缺陷病毒(Human Immunodeficiency Virus,HIV)即艾滋病病毒引起的获得性免疫缺陷综合症(Acquired Immunodeficiency Syndrome,AIDS).HⅣ主要通过性、血液或母婴传播.近年来HIV感染在人群中呈快速增长趋势,经血传播为其主要的感染途径之一.     

毛里塔尼亚育龄期妇女人类免疫缺陷病毒感染情况调查

背景数据报告非洲地区撒哈拉以南的16个国家艾滋病病毒感染者多达2450万.目的了解居于撒哈拉腹地的毛里塔尼亚育龄期妇女人类免疫缺陷病毒的感染及类型,为艾滋病的防治工作提供研究方向和基本资料.设计随机抽样调查.单位苏州大学放射医学与公共卫生学院流行病与卫生统计学教研室,哈尔滨医科大学碘缺乏病研究所,哈尔滨医科大学公共卫生学院流行病与卫生统计学教研室.对象调查于2001-03/2001-06在毛里塔尼亚14个行政区(省)进行,纳入标准毛里塔尼亚14个行政区(省)育龄期妇女,年龄15～49岁,均知情同意.排除标准拒绝调查及非育龄期妇女.总数为331 548名,拟抽样调查4 000～6 000名,抽样率为1.2%～1.8%.方法抽查育龄期妇女,采静脉血、分离血清;用酶联免疫吸附试验做初筛试验,用蛋白印迹试验做确证试验,检测人类免疫缺陷病毒的感染及其类型;用每个行政区人类免疫缺陷病毒感染的检出率乘以该行政区育龄期妇女数,即为该行政区育龄妇女人类免疫缺陷病毒感染的估计人数.主要观察指标检测人类免疫缺陷病毒的感染及其类型;计算不同城市、不同人群的人类免疫缺陷病毒感染率,并加以分析.结果艾卡欧特行政区(省)因故未调查,在13个行政区中抽查了4 648名,抽样率为1.4%.在4 648名15～49岁育龄期妇女中,检出人类免疫缺陷病毒感染者24例,总感染率为0.516%.其中,人类免疫缺陷病毒-1型22例,人类免疫缺陷病毒-2型2例;有5个城市感染率在0.50%～1.01%之间,有3个城市感染率在0～0.50%之间,有5个城市未检出;15～29岁人类免疫缺陷病毒感染23例,占95.83%;在全国13个主要城市中,人类免疫缺陷病毒感染者总数估计在l 400例左右.结论毛里塔尼亚13个主要城市育龄期妇女人类免疫缺陷病毒总感染率为0.516%;人类免疫缺陷病毒感染以人类免疫缺陷病毒-1型为主;人类免疫缺陷病毒感染有地区差异;15～29岁人类免疫缺陷病毒感染占95%以上;毛里塔尼亚艾滋病的流行态势属于传入后的传播扩散阶段.     

人类免疫缺陷病毒检验技术研究进展

人类免疫缺陷病毒(HIV)是引起获得性免疫缺陷综合征和相关疾病的RNA病毒,主要侵犯CD4T细胞、CD4单核细胞和B淋巴细胞。自从人类发现第一例艾滋病患者后,HIV感染者越来越多,据统计,到2004年底,全球有四千万人感染HIV,其中有280～350万人死于艾滋病。最严重的是南     

基质细胞衍生因子1对转染CXCR4基因支气管上皮细胞的增殖和定向趋化作用

背景:早期的诱导替代物表面的气管黏膜上皮覆盖并恢复其功能,是气管替代物研究中的关键问题。基质细胞衍生因子1/CXCR4通路在加快组织修复中发挥重要作用。目的:观察基质细胞衍生因子1对转染CXCR4基因支气管上皮细胞的增殖和定向趋化作用。方法:构建CXCR4慢病毒表达载体并转染人支气管上皮细胞。实验分为3组,空白组:未感染任何病毒的细胞组;对照组:感染未转染CXCR4的慢病毒细胞组;实验组:转染CXCR4慢病毒表达载体的细胞组。将消化好的病毒浸染的人支气管上皮细胞和普通人支气管上皮细胞悬液以不同浓度基质细胞衍生因子1(1μmol/L,100nmol/L,10nmol/L,1nmol/L,0.1nmol/L,0nmol/L)处理。结果与结论:实验成功构建了CXCR4慢病毒表达载体。正常人支气管上皮细胞的CXCR4蛋白基础表达较低。转染CXCR4的人支气管上皮细胞中CXCR4 mRNA和蛋白都有较高水平的表达,且随着基质细胞衍生因子1浓度增加,其吸光度逐渐增加,并呈浓度依赖性(P<0.05)。提示基质细胞衍生因子1增强了转染其受体CXCR4基因支气管上皮细胞的增殖作用和定向迁移能力。     

2012-2019年上海市男男性行为哨点人群HIV-1感染情况及影响因素分析

目的 了解2012-2019年上海市男男性行为人群(MSM)的人类免疫缺陷病毒-1(HIV-1)感染和相关行为情况,探索MSMHIV感染的影响因素,为制定MSM的艾滋病防治措施提供依据.方法2012-2019年对上海市MSM开展哨点监测,采集研究对象静脉血进行HIV、HCV及梅毒抗体检测,用logistic回归模型分析...     

艾滋病的控制和预防

艾滋病(获得性免疫缺陷综合征,简称 AIDS),是机体细胞免疫系统遭到人类免疫缺陷病毒(HI-V)危害而致机体细胞免疫缺陷,继发卡波济氏肉瘤或条件致病性感染为特征的传染病.近年来研究进展迅速,本文仅就关于艾滋病的控制和预防研究扼要综述如下。流行病学1.流行特征,自从1981年美国疾病控制中心首     

毛里塔尼亚育龄期妇女人类免疫缺陷病毒感染情况调查

背景：数据报告非洲地区撒哈拉以南的16个国家艾滋病病毒感染者多达2450万。目的：了解居于撒哈拉腹地的毛里塔尼亚育龄期妇女人类免疫缺陷病毒的感染及类型，为艾滋病的防治工作提供研究方向和基本资料。 设计：随机抽样调查。 单位：苏州大学放射医学与公共卫生学院流行病与卫生统计学教研室，哈尔滨医科大学碘缺乏病研究所，哈尔滨医科大学公共卫生学院流行病与卫生统计学教研室。 对象：调查于2001-03／2001-06在毛里塔尼亚14个行政区（省）进行，纳入标准：毛里塔尼亚14个行政区（省）育龄期妇女，年龄15-49岁，均知情同意。排除标准：拒绝调查及非育龄期妇女。总数为331548名，拟抽样调查4000～6000名，抽样率为1．2％～1．8％。 方法：抽查育龄期妇女，采静脉血、分离血清；用酶联免疫吸附试验做初筛试验，用蛋白印迹试验做确证试验，检测人类免疫缺陷病毒的感染及其类型；用每个行政区人类免疫缺陷病毒感染的检出率乘以该行政区育龄期妇女数，即为该行政区育龄妇女人类免疫缺陷病毒感染的估计人数。主要观察指标：检测人类免疫缺陷病毒的感染及其类型；计算不同城市、不同人群的人类免疫缺陷病毒感染率，并加以分析。 结果：艾卡欧特行政区（省）因故未调查，在13个行政区中抽查了4648名，抽样率为1．4％。在4648名15-49岁育龄期妇女中，检出人类免疫缺陷病毒感染者24例，总感染率为0．516％。其中，人类免疫缺陷病毒-1型22例，人类免疫缺陷病毒-2型2例；有5个城市感染率在0．50％～1．01％之间，有3个城市感染率在0-0．50％之间，有5个城市未检出；15-29岁人类免疫缺陷病毒感染23例，占95．83％；在全国13个主要城市中，人类免疫缺陷病毒感染者总数估计在1400例左右。 结论：毛里塔尼亚13个主要城市育龄期妇女人类免疫缺陷病毒总感染率为0．516％；人类免疫缺陷病毒感染以人类免疫缺陷病毒-1型为主；人类免疫缺陷病毒感染有地区差异；15～29岁人类免疫缺陷病毒感染占95％以上；毛里塔尼亚艾滋病的流行态势属于传人后的传播扩散阶段。     

人胸腺组织原代培养细胞与人类免疫缺陷病毒间的相互作用

背景:人类免疫缺陷病毒能够结合人胸腺的细胞CD4受体,从而导致CD4细胞活性降低。目的:观察人胚胎胸腺组织原代培养与人类免疫缺陷病毒相互作用关系。方法:取人胎胸腺组织进行原代细胞培养,取胸腺的细胞与人类免疫缺陷病毒1ⅢB混合培养设为实验组,设置不加人类免疫缺陷病毒培养的胸腺的细胞为对照组。结果与结论:透射电镜观察显示,培养40h,人类免疫缺陷病毒诱导的胸腺的细胞内即可发现大量艾滋病病毒颗粒。MTT法和免疫组织化学染色检测结果显示,培养40h~22d,HIV诱导胸腺的细胞吸光度值均显著低于对照组(r=0.9733,P<0.05),人类免疫缺陷病毒诱导胸腺的细胞膜上和细胞浆Fas-L阳性表达率均升高(P<0.05)。说明人类免疫缺陷病毒可致原代培养的人胚胎胸腺的细胞活性降低。     

1 例妊娠合并艾滋病孕妇的护理

艾滋病全称为获得性免疫缺陷综合征(acquired immunode ficiency syndrome,AIDS),是由人类免疫缺陷病毒(human immuntxiefidency virus,HIV)感染的性传播疾病[1].目前,中国HIV的流行正处于快速增长期,育龄妇女感染艾滋病的数目正在增加,艾滋病感染的孕妇也在增加.     

Stromal cell-derived factor (SDF) 1-3'A polymorphism may play a role in resistance to HIV-1 infection in seronegative high-risk Thais

OBJECTIVE: It is known that a 32-bp-deleted CCR5 mutant (CCR5-Delta32) plays a critical role in resistance to human immunodeficiency virus type 1 (HIV-1) infection. We became aware of a number of seronegative patients at high risk of HIV-1 infections. Since CCR-Delta32 is not found in Thais, we examined the role of stromal cell-derived factor (SDF) 1-3'A polymorphism in resistance to HIV-1 in seronegative Thai prostitutes at high risk. METHODS: We determined CCR5-Delta32 by PCR, SDF1-3'A by RFLP, and plasma SDF-1 level by sandwich ELISA. RESULTS: We did not find any CCR-Delta32 mutant in 432 subjects. In our SDF1-3'A genotyping, we found allelic frequencies of 0.406, 0.199, and 0.289 in HIV-1-seronegative prostitutes at high risk, HIV-1-seropositive patients, and normal blood donors, respectively. There was a significant difference in the allelic frequencies of SDF1-3'A between HIV-1-seronegative prostitutes at high risk and HIV-1-seropositive patients (p < 0.005). Striking differences were seen in homozygotes (SDF1-3A/3A); 20.3% in HIV-1-seronegative patients at high risk compared with 2.5% in HIV-1-seropositive patients. In addition, we showed that the plasma SDF1 level in the HIV-1-seronegative prostitutes at high risk was twice that found in normal blood donors (p = 0.005), and even higher than that of HIV-1-seropositive patients (p = 0.002). CONCLUSIONS: The finding is relevant as regards the fact that SDF1-3'A polymorphism induces an increase of SDF1 chemokine production, in which it competes with HIV-1 in binding to CXCR4 receptor, and in turn inhibits HIV-1 infection. The SDF1-3'A-mediated resistant mechanism in Thais differs from that of CCR5-Delta32-mediated resistance in Caucasians. This study provides the first evidence for SDF-3'A polymorphism in resistance to HIV-1 infection in Thais, and may represent the resistant mechanism in the extremely rare CCR5-Delta32 mutant of other ethnic groups such as Africans and Japanese.     

Anti-HIV-1 genes; genetic restriction of AIDS pathogenesis by gene variants

Three genes which have variants acting as anti-HIV-1 were described so far. Among three, two are genes encoding receptors for chemokines, namely CCR5 and CCR2, which act as entry coreceptors for HIV-1 virus. The other gene is SDF1 gene. SDF-1, a cytokine belonging to the chemokine family has an inhibitory activity against the HIV-1 infection, because SDF-1 Is the physiological ligand for CXCR4, the entry coreceptor for T tropic HIV-1 virus. Recently, an SDF1 gene polymorphism was figured out to be one of the human genetic factors which regulate the period between the HIV-1 infection and the AIDS onset. By this finding, it was strongly suggested that SDF-1 regulates the onset of AIDS in the actual human population.     

Analysis of CCR5, CCR2, SDF1 and RANTES gene polymorphisms in subjects with HIV-related PML and not determined leukoencephalopathy.

Progressive Multifocal Leukoencephalopathy (PML) is a fatal demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV), a human polyomavirus that can lytically infect and destroy the oligodendrocites in immunosuppressed individuals. After the introduction of highly active antiretroviral therapy (HAART) for AIDS treatment, a PML-like leukoencephalopathy, known as non-determined leukoencephalopathy (NDLE), has also been observed. Since a number of host genetic factors have been identified as having an impact on susceptibility to HIV-1 infection and in the progression to AIDS and death, in this work we analysed the pattern of distribution of different chemokine and chemokine receptor polymorphisms that seem to be involved in HIV+ neurological diseases. The CCR5, RANTES, CCR2 and SDF1 genes were molecularly analysed in 84 HIV+ HAART treated subjects: 55 without neurological disorders (HIV+), 12 HIV+ NDLE and 17 HIV+ PML patients. The RANTES -403 G/A polymorphism was significantly associated with NDLE. These data suggest that mutation of the RANTES allele can predispose to the induction of demyelination similarly to what has been observed in Multiple Sclerosis (MS) and may suggest a possible explanation for the development of leukoencephalopathy without detection of JCV.     

Isolation of HIV-2 from AIDS patient in Ghana and analysis of sero-reactive patterns of Ghanaian sera

Institute for Virus Research, Kyoto University, and Noguchi Memorial Research Institute in Ghana jointly isolated HIV-2 from a Ghanaian AIDS patient. Ghanaian HIV-2[GH-1] was similar in genomic organization to, but different in Restriction Enzyme Maps from the first isolated case, French LAV-2 (HIV-2ROD). This fact is significant in suggesting multiplicity of HIV-2 virus. HIV-2[GH-1] was different from LAV-2 in its antigenicity of envProtein. Sero-reactive patterns of 125 Ghanaians including 57 AIDS/ARC patients were analyzed using HIV-1, HIV-2, and SIVAGM as antigen. 4 groups were recognized. Group I was HIV-1 only positive; Group II, HIV-2-only positive; Group III, mixed HIV-1 and HIV-2 positive; Group IV reacted to gag protein of HIV-1, HIV-2 and SIVAGM but not to envProtein of any. 24 Ghanians were HIV-1 positive; 38 were HIV-2 positive. 19 out of 20 HIV-2-only positive patients were AIDS/ARC patients. Symptoms and route of infection from HIV-1 and HIV-2 AIDS seem to be similar but HIV-2 is weaker pathologically and in communicability. HIV positive patients were mostly found in the big city such as Accra among young women, especially prostitutes who were migratory "workers" in neighboring countries along the Ivory Coast. Sero-reactive patterns of Ghanaians with SIV as antigen had been known for some time to be different from those of Kenyans in the east coast and those of Gabonese. While KEnyan's antibody was high for HIV-1 and lower for SIVAGM, Ghanian's was higher for SIVAGM than HIV-1. Gabonese's was in between. With discovery of LAV-2 (HIV-2ROD) and Ghanian hybridization with its DNA probe Ghanaian's was found to have among other things VPX and VPR in common with HIV-2ROD.     

Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics

To gain more insight into the role of HIV-1-specific cytotoxic T lymphocytes (CTL) in the pathogenesis of AIDS, we investigated temporal relations between HIV-1 Gag-specific precursor CTL (CTLp), HIV-1 viral load, CD4+ T cell counts, and T cell function. Six HIV-1-infected subjects, who were asymptomatic for more than 8 yr with CD4+ counts > 500 cells/mm3, were compared with six subjects who progressed to AIDS within 5 yr after HIV-1 seroconversion. In the long-term asymptomatics, persistent HIV-1 Gag-specific CTL responses and very low numbers of HIV- 1-infected CD4+ T cells coincided with normal and stable CD4+ counts and preserved CD3 mAb-induced T cell reactivity for more than 8 yr. In five out of six rapid progressors Gag-specific CTLp were also detected. However, early in infection the number of circulating HIV-1-infected CD4+ T cells increased despite strong and mounting Gag-specific CTL responses. During subsequent clinical progression to AIDS, loss of Gag- specific CTLp coincided with precipitating CD4+ counts and severe deterioration of T cell function. The possible relationships of HIV-1 Gag-specific CTLp to disease progression are discussed.     

Macrophage-tropic HIV induces and exploits dendritic cell chemotaxis

Immature dendritic cells (iDCs) express the CC chemokine receptor (CCR)5, which promotes chemotaxis toward the CC chemokines regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. By contrast, mature DCs downregulate CCR5 but upregulate CXC chemokine receptor (CXCR)4, and as a result exhibit enhanced chemotaxis toward stromal cell-derived factor (SDF)-1alpha. CCR5 and CXCR4 also function as coreceptors for macrophage-tropic (M-tropic) and T cell-tropic (T-tropic) human immunodeficiency virus (HIV)-1, respectively. Here, we demonstrate chemotaxis of iDCs toward M-tropic (R5) but not T-tropic (X4) HIV-1. Furthermore, preexposure to M-tropic HIV-1 or its recombinant envelope protein prevents migration toward CCR5 ligands. The migration of iDCs toward M-tropic HIV-1 may enhance formation of DC-T cell syncytia, thus promoting viral production and destruction of both DC and T helper lymphocytes. Therefore, disturbance of DC chemotaxis by HIV-1 is likely to contribute to immunosuppression in primary infection and AIDS. In addition, migration of iDCs toward HIV-1 may aid the capture of R5 HIV-1 virions by the abundant DC cell surface protein DC-specific intercellular adhesion molecule (ICAM)3-grabbing nonintegrin (DC-SIGN). HIV-1 bound to DC cell-specific DC-SIGN retains the ability to infect replication-permissive T cells in trans for several days. Consequently, recruitment of DC by HIV-1 could combine with the ability of DC-SIGN to capture and transmit the virus to T cells, and so facilitate dissemination of virus within an infected individual.     

我国237例未接受抗病毒治疗的HIV/AIDS患者中原发性基因型耐药监测和病毒亚型分析

目的 分析237例HIV/AIDS患者中原发性耐药的发生率和病毒亚型分布情况.方法 从河南、云南、上海等20个地区采集237例未经抗病毒治疗的HIV/AIDS患者血浆HIV-1进行基因测序,通过病毒亚型分析软件REGA HIV-1 Subtyping Tool确定测序样本的HIV-1亚型,并与斯坦福大学HIV耐药数据库比对确定测序样本HIV-1耐药相关突变位点.采用b-DNA方法检测患者血浆病毒载量,采用流式细胞仪检测CD4+ T淋巴细胞计数.结果 237例未接受抗病毒治疗的HIV/AIDS患者感染的HIV-1毒株分布为A1、B、C、CRF01-AE、CRF02-AG、CRY7-BC、CRF08-BC、CRF12-BF、G等9个不同亚型,可能的感染时间分布在1990-2006年.237例患者中仅有3例分别对核苷类逆转录酶抑制剂高度耐药、蛋白酶类抑制剂低度耐药和非核苷类逆转录酶抑制剂高度耐药,原发性耐药的发生率为1.3%(3/237).结论我国部分地区未经抗病毒治疗的HIV/AIDS患者中HIV-1原发性基因型耐药的发生比例处于较低水平,病毒亚型分布在9个亚型.     

云南省2006年HIV-1流行毒株的基因测定

目的 为了研究在中国云南流行的艾滋病毒I型(HIV=1)流行毒株的亚型类型与变异特征,进行分子流行病学研究,为艾滋病预防控制工作提供参考.方法 血浆来源于云南省监测系统中的19例HIV-1感染者.采用逆转录聚合酶链反应(RT-PCR)法,从19例患者血清中扩增HIV-1pol-gag共同拥有区片段并直接进行序列测定,所得序列用BioEdit和Mega软件进行亚型及系统发生树分析.结果 19例标本结果显示,12例为CRF08-BC、3例为CRF07-BC、1例为B型、3例为CRF01-AE型.19例毒株间的基因离散率都比较小,CRF08-BC亚型毒株间的基因离散率为2.45%,CRF07-BE亚型毒株间的基因离散率为2.16%;B亚型毒株为5.00%;CRF01-AE亚型毒株与来自泰国的流行CRF01-AE毒株AB032741、U51189的基因离散率分别为3.12%、3.22%.结论 上述结果表明,云南地区CRF-BC重组亚型已成为HIV-1流行病学优势亚型,结果基本上反映了我国HIV-1分子流行病学现状.     

广西壮族人群HIV协同受体CCR5基因突变的检测

目的了解广西壮族人群中HIV协同受体CCR5△32等位基因突变频率和多态性的特点,为评估广西壮族人群对HIV的遗传易感性和艾滋病的防治提供理论依据。方法以152例壮族大学生为研究对象,应用PCR和DNA直接测序等方法检测CCR5及CCR5△32突变体。结果未发现CCR5△32等位基因。结论由于未发现CCR5△32,推测广西壮族人群对HIV-1病毒感染可能具有较大的遗传易感性。