2008年诺贝尔生理学或医学奖与艾滋病毒的发现

艾滋病（AIDS）被称为“世纪瘟疫”。艾滋病毒的发现是生命科学史上的重要事件。围绕谁是艾滋病毒的最早发现者曾有一段争论。这场争论虽然在20世纪90年代中期落下帷幕,但2008年的诺贝尔生理学或医学奖才算划上一个圆满的句号。对艾滋病毒的发现过程和历史上的争论作简明的介绍。     

艾滋病毒监测装置研制成功

澳大利亚墨尔本伯内特研究所研制成功艾滋病毒监测装置。该监测装置无需任何实验室设备,在30分钟内发现患者是否需要抗逆转录病毒治疗。该系统低成本、点护理,特别适合远程医疗,因此而获得发明奖。     

FASEB：研究揭示宿主细胞限制艾滋病毒复制新机制

中科院上海巴斯德研究所王建华研究组在最新研究中,揭示了宿主细胞限制艾滋病毒Ⅰ型（HIV-1）复制的新机制。相关研究成果于7月发表在国际期刊《美国实验生物学会联合会会志》（The FASEB Journal）上。     

纳米颗粒与生物大分子的相互作用及其生物毒性机制

纳米颗粒已得到广泛的应用,同时其潜在的毒性及生物学效应也引起了广泛的关注。许多文献证实纳米颗粒对生物体具有毒性作用,但在分子水平上对其毒性机制的研究较少。本文对近年来纳米颗粒与生物大分子相互作用的最新研究进行了综述,包括纳米颗粒与蛋白质、脂类、核酸等生物分子间的相互作用。     

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。     

艾滋病毒制成疫苗可预防流感

伦敦大学免疫学教授玛丽·科林斯进行的试验表明：艾滋病毒也是可以用来治病的。机制是将艾滋病毒输送到人体的T细胞中,从而激发T细胞抵抗侵入人体的病毒病菌。研究人员曾经使用一种改良的艾滋病毒成功治愈了2名小男孩致命的肾上腺脑白质营养不良症（ALD）。     

噬菌体与细菌相互作用的分子机制研究进展

噬菌体与细菌是自然界中存在最广泛的两类微生物,两者在群体水平、个体水平以及分子水平上均存在复杂的相互作用关系.细菌能够影响溶原性噬菌体的溶原-裂解决策,而被噬菌体感染的细菌基因表达谱也会受到噬菌体影响,使宿主菌的代谢、应激、抵抗力、毒性等多种性状发生改变.现从细菌和噬菌体两者的角度,分别综述细菌抵抗噬菌体感染以及噬菌体...     

萘磺酸衍生物抑制艾滋病毒增殖

美国科研人员已测定萘磺酸衍生物有效抑制人免疫缺陷症病毒(艾滋病病毒,HIV)的增殖,这种衍生物在接受治疗剂量范围的适当浓度是有效的,并只产生一点不愉快的副效应,为此很寄希望此衍生化合物用于治疗艾滋病。     

GBV-C/HIV共感染对AIDS疾病进程和HIV病毒复制的影响

近年来,一些研究发现,GBV-C/HIV共感染可延缓HIV感染疾病的进程,然而也有一些研究得出不同的结论.本研究收集我国安徽省阜阳市HIV血清学阳性的既往献血员血浆标本,对其进行GBV-C感染的检测,研究GBV-C/HIV共感染与HIV病毒载量和CD4 T淋巴细胞绝对计数的关系.用RT-PCR和酶联免疫法检测,在203人中检出GBV-C感染52例,显示该人群GBV-C的感染率为25.6%,男性感染者(35例,67.3%)高于女性感染者(17例,32.7%).分析发现,GBV-C感染与未感染两组患者的CD4 T淋巴细胞绝对计数和HIV病毒载量数据均无统计学差异.本研究中的HIV-1感染者均未接受ART治疗,因而排除了治疗对疾病进展的影响.研究结果显示,在HIV-1感染晚期的献血人群,GBV-C/HIV共感染对CD4细胞和病毒复制水平无显著影响.由于本研究对象中无HIV-1早期感染者,因而不能判断GBV-C在HIV-1感染的早期对疾病进展有无影响.     

Passive immunotherapy in advanced HIV infection and therapeutic plasmapheresis in asymptomatic HIV-positive individuals: a four-year clinical experience

We have been treating patients with advanced HIV disease using passiveimmunotherapy (PIT). Earlier studies of PIT which have been publishedconcerned relatively short periods of treatment: our study is by far the longest and reports also on the long-term effects of plasmapheresis onhealthy HIV-infected individuals. Fifty-nine patients with an average CD4+T-cell count of 55 per cu.mm. at baseline were transfused at monthlyintervals with 500 ml of hyperimmune plasma. No disease progression ordeath occurred among the 8 asymptomatic patients under the treatment, whichlasted for 36.25 months on average. Seven of the 15 ARC patients progressedto AIDS but none died in an average period of 25.9 months. Seven of the 36symptomatic AIDS patients with advanced disease died in an average period of19.6 months. PIT appears to be nontoxic and to have beneficial effectslasting at least four years under continuous treatment. It probably delaysdisease progression in ARC and AIDS patients, and almost certainly does soin asymptomatic late HIV infection with a very low CD4+ T-cell count. Noneof the 51 donors suffered adverse effects, nor did any progress to ARC orAIDS in an average period of 30.1 months. Their laboratory parametersindicated a nearly stable condition: in particular, their average CD4+T-cell count rose from 478 to 498. The study of our plasma donors indicatedthat repeated and frequent plasma donation by asymptomatic HIV-infectedindividuals could delay disease progression, although further studies areneeded to investigate this.     

Targeting to the HIV-1 RRE of the influenza virus NS1 protein effector domain as a potent, specific anti-HIV agent

The Rev axis of HIV autoregulation is one of two critical viral regulatory pathways required for expression of viral genomic and mRNA and for replication. Consequently it is an attractive therapeutic target. Previous studies have investigated the anti-HIV efficacy of targeting to the RRE (the viral RNA target sequence of the Rev axis) a trans-dominant negative inhibitor mutant Rev, M10. In this study we have fused a portion of the influenza virus NS1 protein (which normally inhibits polyA(+) mRNA transport and splicing) to the Rev M10 gene while deleting the NS1 poly(A) binding region. The resulting chimera demonstrates specific and enhanced inhibition of viral-RRE-containing RNA expression.     

Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products

This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC₅₀) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC₅₀: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.     

抗HIV活性木脂素类化合物研究进展

木脂素类化合物具有多种药理活性,其抗HIV机制是通过影响HIV复制周期的某个环节,从而抑制病毒的复制和感染。按其抗HIV检测方法不同,将木脂素类化合物分成4类,本文对1990～2011年有关抗HIV活性木脂素类化合物研究文献进行综述。     

Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: a lead HIV protease inhibitor

With the insight generated by the availability of X-ray crystal structures of various 5,6-dihydropyran-2-ones bound to HIV PR, inhibitors possessing various alkyl groups at the 6-position of 5,6-dihydropyran-2-one ring were synthesized. The inhibitors possessing a 6-alkyl group exhibited superior antiviral activities when compared to 6-phenyl analogues. Antiviral efficacies were further improved upon introduction of a polar group (hydroxyl or amino) on the 4-position of the phenethyl moiety as well as the polar group (hydroxymethyl) on the 3-(tert-butyl-5-methyl-phenylthio) moiety. The polar substitution is also advantageous for decreasing toxicity, providing inhibitors with higher therapeutic indices. The best inhibitor among this series, (S)-6-[2-(4-aminophenyl)-ethyl]-(3-(2-tert-butyl-5-methyl-phenylsulfanyl)-4-hydroxy-6-isopropyl-5,6-dihydro-pyran-2-one (34S), exhibited an EC₅₀ of 200 nM with a therapeutic index of >1000. More importantly, these non-peptidic inhibitors, 16S and 34S, appear to offer little cross-resistance to the currently marketed peptidomimetic PR inhibitors. The selected inhibitors tested in vitro against mutant HIV PR showed a very small increase in binding affinities relative to wild-type HIV PR. C_max and absolute bioavailability of 34S were higher and half-life and time above EC₉₅ were longer compared to 16S. Thus 34S, also known as PD 178390, which displays good antiviral efficacy, promising pharmacokinetic characteristics and favorable activity against mutant enzymes and CYP3A4, has been chosen for further preclinical evaluation.     

蛋白质的错误折叠与疾病

蛋白质是生物体内一切功能的执行者.人体内的任何功能,从催化化学反应到抵御外来侵略都是蛋白质作用的结果.蛋白质折叠是生命活动的最基本过程,近年发现蛋白质的错误折叠可以导致一些疾病.蛋白质的错误折叠与疾病的关系已成为分子生物学新的研究前沿.介绍了细胞内保证蛋白质正常功能的“质量控制”系统,重点讨论了翻译后的质量控制、与蛋白质错误折叠有关的一些疾病和治疗这一类疾病的原则方法.