人免疫缺陷病毒/艾滋病细胞免疫疫苗研究进展

由于人免疫缺陷病毒(HIV)具有变异快、亚型多、攻击免疫系统等特殊的生物学特点,HIV/艾滋病疫苗至今尚未研制成功。20多年来,艾滋病疫苗研究主要采用中和抗体为主和细胞免疫为主等两种策略,然而目前仍没有实质性突破。诱发广谱有效的强CD8+T细胞反应是研制有效HIV疫苗的重要策略。以次要保护性抗原为靶抗原、优化目的基因表达、多抗原联合使用策略,为研究HIV细胞免疫疫苗引入了新的思路。综合分析这些进展,对于重新思考艾滋病疫苗的研究策略可能会有所帮助。     

1／4世纪的艾滋病毒研究——艾滋病毒的发现获得2008年诺贝尔生理学或医学奖

法国科学家弗朗索瓦丝·巴尔·西诺西和吕克·蒙塔尼因发现艾滋病毒而获得2008年诺贝尔生理学或医学奖。本文简述了艾滋病毒的发现及25年来在HIV起源、致病、治疗和预防领域取得的研究进展。     

艾滋病疫苗的研究动向

<正>艾滋病是一种致死性传染病。针对其病原体HIV的疫苗研究工作一直是全球最为关注的课题之一。尽管HIV原型疫苗在动物模型上的试验结果没有达到人们预期的目标,然而随着有关方面研究的进展,许多人相信研制有效的HIV疫苗还是有可能的。主要取得进展的有以下两个方面:(1)HIV保护性免疫抗原决定簇的研究。(2)慢病毒的原型疫苗在动物模型上的研究。     

人类免疫缺陷病毒疫苗的研究进展

人类免疫缺陷病毒疫苗是控制艾滋病的最佳方法,动物模型证实该病毒疫苗是可行的。人类免疫缺陷病毒中和抗体可达到足够高的水平以预防该病毒感染,但有型特异性,人类免疫缺陷病毒特异性细胞毒T淋巴细胞不能单独预防该病毒感染,但能将病毒血病控制在低水平,目前,人们研究重点集中于病毒特异性抗性体和T细胞反应。现有疫苗尚不能诱导对原发性病毒株具有广泛中和能力的抗体。然而,重组痘病毒疫苗和DNA疫苗提示细胞毒T淋巴细胞反应对来自不同进化分支的原发病毒株有广泛的交叉反应力,人们需找到新的免疫原来诱导中和抗体,以取得最佳细胞毒T淋巴细胞反应。     

科学家开发出实验性猿类艾滋病病毒疫苗

美国研究人员开发出一种实验性猿类免疫缺陷病毒疫苗,可大幅降低恒河猴感染猿类艾滋病病毒的风险。这一研究成果为开发人类艾滋病疫苗提供了新思路。研究显示,与注射安慰剂疫苗的恒河猴相比,注射实验性疫苗的恒河猴感染猿类免疫缺陷病毒(SIV)的风险低80%。反复接触病毒后,大部分注射疫苗的恒河猴最终感染猿类免疫缺陷病毒,即猿类艾滋病病毒,但血液中病毒     

In Vitro Modification of Human Immunodeficiency Virus Type 1 (HIV-1) Infectivity by the U937 Cells

The effect of host cell factors on infectivity of human immunodeficiency virus type 1 (HIV-1) was studied by infecting a monoblastoid cell line (U937) or a T-cell line (MOLT-4) with a highly infective single clone of HIV-1 and comparing the infectivity of the produced viruses to different cell lines. Chronically infected U937 cells consistently produced viruses with minimal infectivity. This phenotypic change was host-dependent as the back-passage of the U937-produced low infective viruses into MOLT-4 cells resulted in regaining their original high infectivity. Southern and Northern blot analyses of the HIV-1 grown in U937 cells did not reveal any genomic difference between it and the virus grown it MOLT-4 cells. The radioimmunoprecipitation analysis of viral proteins showed that the HIV-1-infected U937 cells had a different pattern of envelope glycoproteins and core proteins, which well correlated with the low infectivity of the produced viruses. This experimental system using MOLT-4 and U937 cell lines would be useful to further explore host cell factor(s) which play an important role in the regulation of HIV-1 infectivity.     

卡泊芬净联合复方磺胺甲噁唑治疗艾滋病合并肺孢子菌肺炎

目的探讨卡泊芬净联合复方磺胺甲噁唑(TMP-SMX)治疗艾滋病合并肺孢子菌肺炎(PCP)的疗效。方法回顾性总结分析9例艾滋病合并肺孢子菌肺炎的临床资料,包括临床特点及诊疗经过。结果 9例患者临床诊断PCP成立,经卡泊芬净联合TMP-SMX抗PCP治疗后,除1例死亡(老年患者合并慢性支气管炎病史)外,其余8例均得到满意疗效。结论卡泊芬净联合TMP-SMX治疗艾滋病合并PCP,可达到良好的治疗效果。     

两性霉素B联合氟胞嘧啶与伏立康唑治疗艾滋病合并隐球菌脑膜炎的临床回顾性研究

目的观察两性霉素B联合氟胞嘧啶与伏立康唑治疗艾滋病合并隐球菌性脑膜炎的疗效和安全性,探讨艾滋病合并隐球菌性脑膜炎的新型治疗策略。方法采用回顾性病例对照研究,20例艾滋病合并隐球菌脑膜炎分别接受三联治疗（两性霉素B＋氟胞嘧啶＋伏立康唑,n=10）和传统的两联治疗（两性霉素B＋氟胞嘧啶,n=10）,比较两种治疗方案在降低脑脊液中隐球菌计数的幅度以及临床症状缓解、病死率等方面的差异以及不良反应发生情况。结果治疗2周后,三联治疗患者脑脊液中隐球菌计数下降率明显高于两联治疗患者（下降率分别为0.743和0.408,P=0.009）,三联治疗患者头痛明显减轻或消失的时间短于两联治疗者（分别为12 d和20 d,P=0.009）,两组在2周、4周、8周及12周时的病死率均无统计学差异。两种治疗方案的不良反应发生率相当。结论两性霉素B联合氟胞嘧啶与伏立康唑能有效降低脑脊液中隐球菌计数,可作为艾滋病合并隐球菌脑膜炎诱导期的治疗选择。     

Histoplasmosis as cause of penile ulcer in acquired immune deficiency syndrome (AIDS): three case reports

Background Histoplasma capsulatum is the causative agent of American histoplasmosis. The relationship between disseminated histoplasmosis and AIDS has been well established. Widespread hematogenous dissemination of Histoplasma capsulatum in HIV positive patients can cause a plethora of clinical manifestations; virtually any organic system can be affected. However, genital ulceration by H. capsulatum in patients with AIDS is a real challenge during investigation of the infection due to the great variety of differential diagnoses that are involved. Method The diagnosis was performed by histopathologic study; H. capsulatum was detected by silver staining (Grocott staining) and confirmed by immunocytochemistry. Results We report three cases of histoplasmosis in patients with AIDS, in which we observed genital ulcers, an unusual form of presentation of this disease. In one of these cases, the treatment resulted in total cure. Conclusion The cases reported herein are to illustrate the plurality of pathologies and clinical manifestations, which may affect immunocompromised patients. The correct diagnosis of fungal diseases in these patients following well established treatment will improve the prognosis.     

Cryptococcus neoformans: A central nervous system isolate from an AIDS patient that is rhinotropic in a normal mouse model

A strain of Cryptococcus neoformans that was isolated from the cerebrospinal fluid of a human diagnosed as having acquired immunodeficiency syndrome (AIDS), and that produced cutaneous lesions in experimentally infected, normal mice is described. Although no unusual cutaneous manifestations were noted in the patient's records, this isolate of C. neoformans proved to be dermotropic when injected intravenously into CD-1 mice. The LD₅₀ at 28 days post infection ranged from 3.6–7.5×10⁵ cells per mouse, and in vitro growth rate studies demonstrated that this isolate grew well at 35 °C and at 37 °C, but did not grow at 40 °C and higher. This isolate was rhinotropic producing large granulomatous lesions in the nasal tissues. Other cutaneous tissues affected were the periocular tissues, ears, feet and tail, although the granulomas were nodular in structure and less necrotic than the nasal lesions. The brain, lungs, liver, kidneys and spleen also were culture positive for C. neoformans. Histopathologically, each affected tissue examined had large densities of yeast cells and a chronic, granulomatous host response. Animals surviving the infection appeared to develop a commensal-type relationship with the infective yeast. This is the first report of an isolate of C. neoformans from an AIDS patient that has caused cutaneous manifestations in an animal model. The model described in this report may be useful for elucidating pathogenic mechanisms of cryptococcosis, particularly cutaneous manifestations of the disease.     

On transient effects in the HIV/AIDS epidemic

During the initially exponential spread of the human immunodeficiency virus (HIV—the causative agent of AIDS) the growth rate of the number of AIDS cases decreases from plus infinity to the growth rate of HIV infections. A sensitivity analysis shows that for all reasonable values of the parameters of the HIV epidemic (incubation period, initial doubling time, etc.) the effect of this positive transient becomes negligible when the annual number of AIDS cases reaches a few dozen. Necessary and sufficient conditions are given for the growth rate of the number of AIDS cases to be monotonically decreasing during the positive transient. A mildly pathological density function for the incubation period of AIDS provides an example of a growth rate of AIDS that does not decrease monotonically, even though HIV is spreading exponentially. A negative transient occurs when the growth rate of HIV begins to decrease. In this context a somewhat surprising result emerges under the assumption that the growth rate of HIV is non-increasing: the growth rate of AIDS is at all times larger than the growth rate of HIV. A logistic HIV epidemic illustrates this result, and implications for the growth of the HIV epidemic in the United States and Europe are discussed. In particular, it is shown that the positive transient must have passed by 1982 in the United States and by 1986 or 1987 for the five European countries with the largest caseloads.     

HIV(+)/AIDS并发肺结核与单纯肺结核患者临床对照分析

提高对HIV(+)/AIDS并发肺结核临床表现的认识。方法:选取1998年以来我院收治的HIV(+)/AIDS并发肺结核的病例共47例为观察组(A组),及同期住院的HIV(-)单纯肺结核病例50例为对照组(B组)进行回顾性对照分析。结果:(1)A组发烧和体重下降较B组更常见,而咳嗽和咯血较B组少见;(2)A组痰抗酸杆菌阳性率显著低于B组;(3)A组结核杆菌培养阳性率显著低于B组,而耐多药结核(MDR-TB)所占比率显著高于B组;(4)肺结核的X线表现为弥漫性浸润或粟粒性阴影的,A组多于B组,而A组影像学空洞率显著低于B组;(5)A组合并肺外结核较B组多见,A组淋巴系统较B组常发生结核病变,A组全身血液播散性结核病的发病率明显高于B组;(6)PPD结核菌素反应阳性率A组显著低于B组,A组PPD阳性率与外周CD4+T淋巴细胞数相关。结论:HIV(+)/AIDS患者并发肺结核临床表现不典型。     

The role of HIV replicative fitness in perinatal transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selective pressure in the perinatal transmission of HIV-1 is maternal neutralizing antibodies.Recent studies have shown that viruses which are successfully transmitted to the child have growth advantages over those not transmitted,when those two viruses are grown together.Furthermore,the higher fitness is determined by the gp120 protein of the virus envelope.This suggests that the selective transmission of viruses with higher fitness occurred exclusively,regardless of transmission routes.There are many factors contributing to the selective transmission and HIV replicative fitness is an important one that should not be neglected.This review summarizes current knowledge of the role of HIV replicative fitness in HIV MTCT transmission and the determinants of viral fitness upon MTCT.     

The Role of HIV Replicative Fitness in Perinatal Transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selectiv...