作者：David Heckerman 微软研究院eScience组
人类抗击艾滋病毒和艾滋病的斗争至今已达数十年之久，而研究人员却一直困惑于这种病毒。
数十年来，人类一直与艾滋病毒相抗争。但是，这种病毒总是有能力躲避人类免疫系统的攻击，这令研究人员们感到很困惑。
通常，感染了病原体的人类细胞会在其表面显现出病原体肽（the pathogen peptides）的特征片段，它们被称为抗原表位（epitopes），人体免疫系统可以识别它们，并引发免疫反应。艾滋病毒感染的细胞也会产生这些抗原表位，但由于艾滋病毒极容易发生变异，其抗原表位也是如此，从而引发人体免疫系统和艾滋病毒之间旷日持久的斗争。因此，科学家一直渴望更好地了解艾滋病毒感染者产生抗原表位的过程，希望籍此找到打赢这场战斗的途径。
通过近来对受感染细胞中艾滋病毒蛋白质降解过程的研究，人们对艾滋病毒抗原表位的呈现过程有了更新的深入了解。这一重要研究是由拉贡研究所（由马萨诸塞州总医院（Massachusetts General Hospital）、麻省理工学院和哈佛大学联合建立）的一个团队进行的，其中也包括微软研究院eScience组Carl Kadie和我本人所贡献的绵薄之力。论文已于2011年5月9日发表在《临床研究》("JCI", Journal of Clinical Investigation)的网站上，6月份的JCI印刷版刊物还将会刊登该文。
拉贡研究团队由Sylvie Le Gall领导，成员包括Estibaliz Lazaro，Pamela Stamegna， Shao Chong Zhang， Pauline Gourdain，Nicole Y. Lai， Mei Zhang和Sergio A. Martinez，他们探究了人体细胞质中艾滋病毒短肽（short HIV peptides）的稳定性。研究发现，这些艾滋病毒衍生肽（HIV-derived peptides）的稳定性千差万别：有一些在几秒钟内就降解，而另一些则在一小时后仍然基本完好。
拉贡研究团队注意到，肽物质稳定性是决定细胞表面出现多少表位的关键性因素：受感染细胞质中的肽降解得越少，其表面出现的表位就会越多。
接着，Carl和我对166种经检测的艾滋病毒肽残留物进行了计算分析，寻找能够描述稳定肽及非稳定肽的具体生化特征。由此，我们将能够识别多种图案或模式，并得以推断某种特定抗原表位的稳定性或不稳定性。一个基于本研究结果开发而成的推断工具已经发布到网上。
那么，推断抗原表位的稳定性有何意义呢？要回答这个问题，我们首先需要知道，一些研究人员认为，艾滋病毒同时拥有保护性和非保护性抗原表位（protective and non-protective epitopes）。当被感染细胞受到免疫系统攻击时，保护性抗原表位会迫使病毒变异成为一个无法生存的形态，以保护患者不受慢性艾滋病毒的感染。非保护性抗原表位则相反，它们不会诱发保护性免疫反应。我们还需要了解，抗原表位具有交叉反应（cross-reactive）的特性，这就是说，当免疫系统学会打击特定抗原表位时，它还能够识别和攻击类似的抗原表位。因此，假设我们知道艾滋病毒抗原表位X是保护性的，但是不稳定，那么就意味着它不会大量生产，因此不大可能成为免疫反应的关键目标。但如果运用我们的研究结果，就可以找出能够与抗原表位X产生交叉反应而且更加稳定的抗原表位X-prime，进而以X-prime为基础开发疫苗，后者可以触发同时针对X和X-prime的强烈免疫反应。这将帮助免疫系统更有效地打击带有X抗原表位的艾滋病毒感染细胞，从而削弱病毒的危害。
我们与拉贡研究所通过合作共同发现了一条新的路径，以更好地帮助人们利用艾滋病毒的片段激活免疫系统，并有望设计出一种可以有效防疫艾滋病毒的疫苗。此举意义重大且富有成效。
艾滋病不治会早死，早治才康复 艾滋病不治会早死，早治才康复 艾滋病不治会早死，早治才康复 艾滋病不治会早死，早治才康复
 |
| 图示∶2011年5月正式出版的《中国特色医疗金鉴》登载的刘君主任及其机构事迹 |
| |
|
|
Armed immune system against HIV
(2011-06-30 09:23:55)
The human fight against HIV and AIDS fight has now been for decades, scientists have been eager to better understand the HIV epitopes generated in the process in hopes of finding ways to win this battle. Microsoft Research's eScience group aragon Institute of cells infected by the HIV protein degradation in the process of research on HIV epitope presentation has been updated in-depth understanding of the process. The study is expected to help people use pieces of HIV activates the immune system, can design an effective prevention of HIV vaccines.
Author: David Heckerman Microsoft Research eScience group
The human fight against HIV and AIDS fight has now been for decades, but researchers have been puzzled in the virus.
For decades, mankind has to struggle with HIV. However, the virus always have the ability to evade the human immune system attack, which the researchers were confused.
Normally, human cells infected with the pathogen's surface, revealing in its pathogen-peptide (the pathogen peptides) characteristic fragments, which are known as epitopes (epitopes), the body's immune system can recognize them, and trigger an immune response. HIV-infected cells also produce these epitopes, but because HIV mutates very easily, and its epitope is also true, thus triggering the body's immune system and the protracted struggle between HIV. Therefore, scientists have been eager to better understand the HIV epitopes generated in the process in hopes of finding ways to win this battle.
Recently, the infected cells by the HIV protein degradation in the process of research, people living with HIV epitope presentation has been updated in-depth understanding of the process. This important study by the Institute of aragon (by the Massachusetts General Hospital (Massachusetts General Hospital), Massachusetts Institute of Technology and Harvard University jointly established) of a team, which also includes Microsoft Research eScience group Carl Kadie and I I contributed modest. Papers was May 9, 2011, published in "Clinical Research" ("JCI", Journal of Clinical Investigation) website, June JCI print publications also will be published in the paper.
Aragon research team led by the Sylvie Le Gall, comprising Estibaliz Lazaro, Pamela Stamegna, Shao Chong Zhang, Pauline Gourdain, Nicole Y. Lai, Mei Zhang and Sergio A. Martinez, they explore the human body in the cytoplasm of HIV peptide (short HIV peptides) stability. The study found that the HIV-derived peptides (HIV-derived peptides) stability vary widely: some degradation within a few seconds, while others are one hour remains largely intact.
Aragon research team noted that the peptide is to determine the physical stability of the number of cell surface epitope of the key factors: the infected cytoplasm in the less degradation of the peptides, their surface epitopes with it.
Then, Carl and I are 166 kinds of tested HIV peptide residues were calculated and analyzed, looking for ways to describe the stability of peptide and non-stable peptide specific biochemical characteristics. As a result, we will be able to identify a variety of patterns or models, and to infer a particular epitope of the stability or instability. Based on the results of a research tool developed with the inference has been published to the web.
Then, infer the stability of epitope point? To answer this question, we first need to know, some researchers believe that HIV have both protective and non-protective epitopes (protective and non-protective epitopes). When the infected cells by the immune system attack, protective epitopes will force the virus mutates into a form can not survive, to protect patients from chronic HIV infection. Non-protective epitopes on the contrary, they do not induce a protective immune response. We also need to understand, with cross-reactive epitopes (cross-reactive) properties, that is, when the immune system learn to fight against a specific epitope, it also can identify and attack similar to the epitope. Therefore, if we know that HIV epitope X is protective, but unstable, then it means that it will not be mass produced, so the immune response is unlikely to become a key target. However, if the use of our findings, we can identify with the epitope can cross-react with X and more stable epitope X-prime, then the X-prime-based vaccine development, which can be triggered simultaneously for X and X-prime strong immune response. This will help the immune system to more effectively combat with X epitopes of HIV-infected cells, thus weakening the dangers of the virus.
Through our Institute in collaboration with aragon found a new path to better help people use pieces of HIV activates the immune system, and can be expected to design an effective prevention of HIV vaccines. This is significant and fruitful.
