HIV病发病学新概念：肠淋巴组织主要病灶论

艾滋病 (acquiredimmunodeficiencysyndrome ,AIDS)无疑是人类空前严重的疾病 ,这不仅仅因为它是一种流行范围最广的传染病 ,而且它还是一种死亡率几乎高达 10 0 %的疾病。人免疫缺陷病毒病(humanimmunodeficiencyvirusdisease ,HIVdisease)指从HIV感染到AIDS发病整个病程 ,HIV     

中国HIV-1病毒分离株的生物学特性与疾病进展关系的研究

目的　从HIV AIDS患者应用微量全血法分离中国HIV 1毒株 ,研究HIV 1的生物学特性与HIV AIDS疾病进展相关性。方法　建立微量全血法 ,从HIV AIDS全血标本中分离 17株HIV 1病毒分离株 ;检测这 17株病毒分离株嗜性和复制动力。结果　从 2 6例HIV AIDS病例中分离出HIV 1病毒 ,分离率为 6 5 .4 % (17 2 6 ) ,其中 17例HIV 1感染者的病毒分离率为 5 2 .9% (9 17) ,均为巨噬细胞嗜性 (M嗜性 ,NSI) ;9例AIDS患者的HIV 1病毒分离率为 88.9% (8 9) ,其中 7株为T细胞嗜性 (T嗜性 ,SI) ,1株为巨噬细胞嗜性。通过检测P2 4抗原确定 17株HIV 1病毒分离株的复制动力。在分离到的 17株HIV 1中 ,SI型病毒分离株与AIDS组显著相关 (P <0 .0 5 ) ;AIDS期的病毒分离株的复制动力明显高于HIV感染期 (P <0 .0 5 )。结论　微量全血法可用于病毒分离。 17株分离株的HIV 1复制动力与CD4 + T淋巴细胞计数呈线性负相关 ,与病毒载量呈正相关。     

HIV-1Nef蛋白变异对艾滋病疾病进展影响机制的研究

人类免疫缺陷病毒(HIV-1、HIV-2)和猴免疫缺陷病毒(SIV)的Nef基因与病毒致病性有关,在疾病进展到AIDS期的过程中发挥重要作用。Nef可通过提高病毒颗粒感染性、激活CD4淋巴细胞及防止受感染细胞凋亡等多种途径促进HIV复制[1];Nef表位缺失可形成HIV免疫逃逸株,影响机体针对HIV病毒的免疫反应。Nef基因对HIV感染后AIDS疾病进展的影响机制至今仍无定论,本文就近年来此方面的研究,作一简要回顾。     

艾滋病患者心理状态分析及对策

<正>山西省艾滋病定点收治单位先后收治人免疫缺陷病毒(HIV)感染者/获得性免疫缺陷综合征(AIDS)患者55例,针对他们存在的心理问题及其特点进行干预和治疗效果明显,现报告如下。1HIV感染者/AIDS患者负性心理分析1.1疾病本身:一旦感染HIV,感染者就会产生比患任何疾病都严重、复杂的心理障碍,这种负性情绪一方面来自HIV/     

HIV/AIDS患者B7-H1的表达与合并机会性感染关系的研究

目的:探讨HIV/AIDS患者外周血髓样树突细胞(mDC)上B7-H1表达水平与合并机会性感染的关系。方法:采集2009年1月至2012年5月住院的42例未经抗逆转录病毒治疗(ART)的HIV/AIDS患者及42名健康对照组抗凝全血,用流式细胞仪检测外周血mDC上B7-H1表达水平,并分析其与疾病进展的相关性。结果:HIV/AIDS患者合并机会性感染B7-H1表达水平显著高于未合并机会性感染组(P<0.05),未合并机会性感染组显著高于健康对照组(P<0.05);B7-H1表达水平>30%合并机会性感染率显著高于B7-H1表达水平<10%的HIV/AIDS患者(P<0.05);HIV/AIDS患者mDC上B7-H1表达水平与CD4+T细胞数量显著负相关(r=-0.665,P<0.05),而与病毒载量显著正相关(r=0.604,P<0.05)。结论:HIV/AIDS患者mDC上B7-H1表达水平与合并机会性感染密切相关,是疾病进展的指标。     

HIV感染者/AIDS病人及其家属的焦虑、抑郁状况调查

目的:了解HIV感染者/AIDS病人及其家属的焦虑、抑郁状况及其相关因素,从而为建立HIV感染者/AIDS病人社区综合关怀支持模式、改善HIV感染者/AIDS病人及其家属的心理状况提供客观依据.方法:选择四川省HIV感染率和AIDS患病率较高的两个县(资中县和凉山州昭觉县)作为目标社区,在目标社区内共计调查了71名HIV感染者/AIDS病人及其162名家属和97名健康人群,选用抑郁自评量表(SDS)和焦虑自评量表(SAS)作为调查评定工具,选用生活质量量表(CQOL-74)、社会支持评定量表(SSS)收集相关资料,采用SPSS统计软件进行统计分析.结果:HIV感染者/AIDS病人的SAS和SDS评分高于正常对照(分别为t=5.343,t=5.272,P均＜0.001),已死亡的HIV感染者/AIDS病人家属的SAS和SDS评分高于正常对照(分别为t=4.873,t=5.133,P均＜0.001),HIV感染者/AIDS病人的SAS和SDS评分与疾病状况、物质滥用、社会支持及生活质量存在明显相关性.结论:焦虑和抑郁情绪在HIV感染者/AIDS病人及已死亡HIV感染者/AIDS病人家属中普遍存在,这些负性情绪主要与疾病状况、物质滥用、社会支持及生活质量等因素有关.     

HIV/AIDS的遗传背景及全基因组关联研究

宿主遗传背景是人类免疫缺陷病毒(HIV)感染机体后个体间表型差异的主要影响因素之一.它不仅影响HIV易感性,而且影响获得性免疫缺陷综合征(AIDS)进程.全基因组关联研究(GWAS)是一种在全基因组范围内检测与疾病相关基因的技术方法.目前,共有22项与HIV/AIDS相关的GWAS,发现了多个与HIV感染及AIDS进程相关的易感基因和位点.这些结果对研究宿主遗传背景在HIV感染中的作用、AIDS进程的预测及疫苗的研发都有重要意义.本文将对HIV/AIDS的遗传背景及其相关的GWAS作一综述.     

HIV/AIDS患者NK细胞趋化因子受体表达研究

目的:探讨中国HIV/AIDS患者NK细胞表面趋化因子受体CXCR4、CCR5表达情况。方法:采用流式细胞仪分析HIV/AIDS患者外周血NK细胞表面趋化因子受体CCR5和CXCR4的表达。结果:未治疗典型HIV/AIDS患者NK细胞表面趋化因子受体CXCR4和CCR5与正常对照无显著差异(P >0 0 5 ) ,HIV长期不进展者NK细胞CCR5受体低于未治疗的典型HIV/AIDS患者(P <0 0 5 ) ,与正常对照相比无显著差异(P =0 0 5 ) ;HAART治疗组NK细胞趋化因子受体CCR5表达显著低于未治疗典型HIV/AIDS患者(P <0 0 1)。结论:趋化因子受体CCR5在NK细胞上表达的变化与疾病的不同阶段密切相连,对NK趋化因子受体的检测有助于艾滋病疾病进程的研究     

艾滋病及抗艾滋病病毒药物的进展

艾滋病(获得性免疫缺陷综合征,AIDS)是感染了艾滋病病毒(HIV)所致的一种严重的疾病。HIV为人逆转录病毒即RNA逆转录病毒,病毒的基因信息由RNA通过病毒逆转录酶(RT)传到DNA,再整合进入宿主细胞染色体内变成前病毒而引     

艾滋病实验室检测进展（文献综述）

获得性免疫缺陷综合征(acqlliDed immunodeficiency syn-arome)简称艾滋病(AIDS),是由人类免疫缺陷病毒(humanimmunodeficiency virus,HTV)感染所引起的一种严重的传染性疾病.自1985年第一代HIV/抗体问世以来,HIV病原学检测方法有了长足的进步.     

Translational Mini‐Review Series on Vaccines for HIV: T lymphocyte trafficking and vaccine‐elicited mucosal immunity

Many pathogens use mucosal surfaces to enter and propagate within the host, making particularly desirable vaccines that target immune responses specifically to mucosal compartments. The majority of mucosal vaccine design strategies to date have been empirical in nature. However, an emerging body of basic immunological knowledge is providing new insights into the regulation of tissue‐specific lymphocyte trafficking and differentiation. These insights afford the opportunity for the rational design of vaccines that focus immune responses at mucosal surfaces. Mucosal cellular immunity may prove critical for protection in the context of HIV infection, and thus there has been considerable interest in developing vaccines that target HIV‐specific cellular immune responses to the gastrointestinal and vaginal mucosa. However, the optimal strategies for eliciting mucosal cellular immune responses through vaccination remain to be determined. Here, we review both recent vaccine studies and emerging paradigms from the basic immunological literature that are relevant to the elicitation of potent and protective mucosal cellular immune memory. Increasing the synergy between these avenues of research may afford new opportunities for mucosal vaccine design.     

Functional CD8+ CTLs in mucosal sites and HIV infection: moving forward toward a mucosal AIDS vaccine

The gastrointestinal and vaginal mucosa are the major routes of natural HIV transmission, with the former being the primary reservoir for virus replication. The crucial need for a global HIV vaccine underscores the effort to develop vaccines capable of eliciting mucosal immune responses. Vaccines that induce high levels of effective mucosal immunity should impact viral replication rate and prevent dissemination of virus from the mucosa into the systemic circulation. In our opinion, the major effort for effective HIV vaccine should be concentrated on generating protective immunity at the site of viral entry (i.e. the gastrointestinal and vaginal mucosae). Here we examine the current information regarding the role of mucosal immunity in prevention of HIV transmission and discuss strategies for mucosal AIDS vaccine development.     

Virus-like particles as HIV-1 vaccines

Traditional successful antiviral vaccines have relied mostly on live-attenuated viruses. Live-attenuated HIV vaccine candidates are not ideal as they pose risks of reversion, recombination or mutations. Other current HIV vaccine candidates have difficulties generating broadly effective neutralising antibodies and cytotoxic T cell immune responses to primary HIV isolates. Virus-like-particles (VLPs) have been demonstrated to be safe to administer to animals and human patients as well as being potent and efficient stimulators of cellular and humoral immune responses. Therefore, VLPs are being considered as possible HIV vaccines. Chimeric HIV-1 VLPs constructed with either HIV or SIV capsid protein plus HIV immune epitopes and immuno-stimulatory molecules have further improved on early VLP designs, leading to enhanced immune stimulation. The administration of VLP vaccines via mucosal surfaces has also emerged as a promising strategy with which to elicit mucosal and systemic humoral and cellular immune responses. Additionally, new information on antigen processing and the presentation of particulate antigens by dendritic cells (DCs) has created new strategies for improved VLP vaccine candidates. This paper reviews the field of HIV-1 VLP vaccine development, focusing on recent studies that will likely uncover promising prospects for new HIV vaccines.     

Into the wild: simian immunodeficiency virus (SIV) infection in natural hosts

Identifying distinctions between pathogenic HIV and simian immunodeficiency virus (SIV) infections and nonprogressive SIV in natural African primate hosts might provide key insights into HIV pathogenesis. Similar to pathogenic HIV infection in humans, natural SIV infections result in high viral replication and massive acute depletion of mucosal CD4(+) T cells. A key distinction of natural SIV infections is a rapidly developing anti-inflammatory milieu that prevents chronic activation, apoptosis and proliferation of T cells and preserves the function of other immune cell subsets, thus contributing to the integrity of the mucosal barrier and the lack of microbial translocation from the gut to the peritoneum. Immunologic features observed during natural SIV infections suggest approaches for designing new strategies for producing novel second-generation vaccines and therapeutic approaches to inhibit disease progression in HIV-infected humans.     

AIDS vaccine development: the long and winding road

Development of a vaccine that provides sterilizing immunity against HIV infection remains an elusive goal, due primarily to the difficulty in generating neutralizing antibodies to primary HIV isolates. In lieu of a present solution to this problem, recent approaches to develop vaccines against HIV/AIDS have focused not on preventing infection outright, but on eliciting potent antiviral CD8+ T-cell responses to limit HIV replication in individuals who become infected after vaccination. Successful control of HIV replication in vivo, enabled by vaccine-elicited immune responses should, in turn, attenuate an individual's rate of progression to AIDS while reducing their likelihood of subsequently transmitting HIV. Recent pre-clinical evaluation of CTL-based vaccines in non-human primate models of AIDS has shown several different vaccine modalities (e.g. heterologous 'prime/boost' strategies such as DNA + recombinant viral vectors) to be capable of eliciting high-level cellular immune responses that are associated with limitation of virus replication and protection against disease following challenge with select pathogenic virus isolates. However, it is not currently known to what extent these protective effects, observed under optimal experimental conditions in select animal models, can be translated into relevant protection of humans against AIDS. In this article we discuss the promise, potential limitations, and scientific challenges that currently provide the context for efforts to develop and successfully employ a safe and effective AIDS vaccine.     

Mucosal immunology of HIV infection

Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection, but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of ‘symbiotic’ intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high-level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4⁺ T-cell responses, binding anti-bodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Furthermore, immune therapies specifically directed toward boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients.     

The mucosal immune system: from control of inflammation to protection against infections

The IV meeting of the European Mucosal Immunology Group, held October 8-10, 2004, in Lyon, gathered fundamental and clinical research scientists to discuss the most recent updates on basic and clinical aspects of mucosal immunology. The meeting was focused on innate and acquired immune mechanisms underlying handling and immune recognition of commensals, allergens, and pathogens by the mucosal immune system and its outcome in health and disease as well as for vaccine development. The scientific program featured five topics of growing interest for fundamental research scientists and clinicians, including the role of commensal bacteria in mucosal immunity; function of dendritic cells in infection, inflammation, and tolerance; control of mucosal inflammation by regulatory T cells; novel routes and adjuvants for mucosal vaccines; and mucosal immunity against HIV infection and vaccination strategies.     

Use of Nonhuman Primate Models to Develop Mucosal AIDS Vaccines

The HIV vaccines tested in the halted Step efficacy trial and the modestly successful phase 3 RV144 trial were designed to elicit strong systemic immune responses; therefore, strategies to direct immune responses into mucosal sites should be tested in an effort to improve AIDS vaccine efficacy. However, as increased CD4⁺ T-cell activation and recruitment to mucosal sites have the potential to enhance HIV transmission, mucosal immune responses to HIV vaccines should primarily consist of effector CD8⁺ T cells and plasma cells. Controlling the level of mucosal T-cell activation may be a critical factor in developing an effective mucosal AIDS vaccine. Immunization routes and adjuvants that can boost antiviral immunity in mucosal surfaces offer a reasonable opportunity to improve AIDS vaccine efficacy. Nonhuman primate models offer the best system for preclinical evaluation of these approaches.     

Immunobiology of mucosal HIV infection and the basis for development of a new generation of mucosal AIDS vaccines

Mucosal tissues are the primary site of natural HIV transmission and a major reservoir for HIV replication. Targeting immune responses to the mucosal entry site before viral dissemination could protect and also clear viral reservoirs. Recent understanding of mucosal HIV transmission and of chemokines and integrins in mucosal trafficking can aid design of new strategies to enhance AIDS vaccine efficacy.     

Rethinking globally relevant vaccine strategies to human immunodeficiency virus type-1

According to the latest UNAIDS figures for 1999 there were an estimated 30.6 million people living with HIV-1, with 16,000 new HIV infections per day. The only global strategy of combating new HIV infections is to make a vaccine that is affordable to developing countries, where greater than 90% of new infections occur, and that has enough efficacy to interrupt high rates of transmission. This review critically examines: 1) important immune parameters that should be considered which will allow an understanding of preventative vaccine design and 2) the mechanisms underlying immune destruction during HIV-1 infection that will facilitate design of therapeutic vaccines. A realistic goal of a preventative vaccine is to elicit protective immune responses in vaccinees that would prevent HIV-1 from replicating extensively in the host. Components of protective immunity are thought to include neutralizing antibodies (NAB) and cytotoxic T lymphocytes (CTL). Rethinking vaccine strategies has to take into account that HIV-1 vaccines must elicit primary cellular and humoral immunity via dendritic cell and Langerhan cell priming. It is only under these conditions that boosting immunity with subsequent vaccinations will allow high enough CTL effector cells and NAB titres to impede or to prevent HIV-1 replication. Success of therapeutic vaccine strategies, has to take into consideration the pathology of persistent immune stimulation by chronic HIV-1 infection. To re-stimulate immunity and re-direct immune responses, chronic immune stimulation by HIV-1 has to be alleviated by reducing high levels of viral antigen presentation by suppressing virus with antiretroviral agents. Such treatment courses may only have to be transient, long enough for immunity to respond to an immunogenic stimulus. Short-course drug therapy may then be an affordable option for many countries already carrying a high burden of HIV-1/AIDS.