艾滋病疫苗新希望
2011-06-28作者：果壳网出处：MSN数码IT责编：王和浩
“HIV的发现使我们能够在未来研制出预防艾滋病的疫苗……我们希望大约两年内能够有可用来测试的艾滋病疫苗。”——玛格丽特•赫克勒(Margaret Heckler)，美国卫生与公共服务部部长，1984年4月23日。
27年过去了，到现在人们仍没有研制出艾滋病疫苗。原因很简单，HIV进化的速度太快了。HIV每天大约能产生1000亿个新的病毒粒子，而且这个过程非常不精确。大多数遗传物质的复制都有很高的准确性，但HIV在复制过程中会有大量的错误出现，从而产生一群变异的个体，导致任何针对HIV的药物或疫苗很快就会失效。
为了对付这一不断变化的对手，有些科学家致力于寻找HIV蛋白中一直保持不变的部分。这些“保守区域”在某种意义上是很重要的，它们若发生变异，病毒的复制能力就会减弱。若能训练免疫系统来攻击这些区域，那么病毒只能要么等死，要么变弱。
但是病毒还有第三种选择，它可以修改自身蛋白的其他部分，导致保守区域不再重要，这样它可以躲过免疫系统的防御，而不会对自身造成任何损害。HIV又一次逃脱了。
来自麻省理工学院的文森特•戴希瑞尔(Vincent Dhairel)和卡西克•谢加(Karthik Shekhar)认为我们需要一个新的方法。一项由阿勒普•查克拉博蒂(Arup Chakraborty)和布鲁斯•沃克(Bruce Walker)领导的研究确定了HIV蛋白上的很多保守区域，他们将其称为“HIV扇区”，在病毒其他区域发生变化时这些区域仍全都保持不变。HIV要逃过免疫系统对所有这些区域的攻击，必须要产生许多种不同的变异，这肯定会使它的活力变弱。
这是一个新颖的方法。“它为HIV领域的研究注入了新鲜的血液。”沃克说，他几乎从HIV被发现以来就一直在研究它。“我们讨论这一领域的挑战时，查克拉博蒂认为我们对HIV进化的认识过于狭隘，并提出了这个方法。”
戴希瑞尔和谢加使用了一种叫做“随机矩阵理论”的技术，来确定这些保守区域。这种技术能够检测出变化方式一致的目标群组，它最初来源于高能物理学，后来经济学领域也用它来研究股票价格的波动。这个团队使用这项技术分析了来自一个庞大数据库的病人的HIV蛋白序列。“随机矩阵理论使人们能够分析一种股票与其他股票有何联系。”沃克说，“我们用同样的方式来分析一个区域的进化是否和其他区域的进化有关联，结果是有的。”
他们分析了组成HIV衣壳的Gag蛋白，这种蛋白镶在病毒表面，是免疫系统的攻击目标。戴希瑞尔和谢加确定了Gag蛋白里的五个扇区，每个扇区都包括共同进化的区域，而且在这些区域，很少会发生变异。
在这些扇区中，扇区3较为特殊，它对于将不同的Gag蛋白结合起来发挥着重要的作用。没有它们，病毒就不能组装自己的衣壳。如果这些区域中有一个发生变化，病毒还能应对，但是如果有几个区域发生变化，病毒就会裸露，并且活性下降。
戴希瑞尔和谢加由此推论如果免疫系统能靶向扇区3的几个区域，HIV就会难以进化，即尝试通过将病毒逼进一个进化终端来对付进化得过快的病毒。现实中其实有些人已经做到了这点。
每三百个感染HIV的人中，大约有1人一生都不会得艾滋病，这些人毕生可与病毒共存，但不会发病。戴希瑞尔和谢加发现他们的免疫细胞靶向了扇区3的部分Gag蛋白。这有助于解释是什么让这些人如此特别。他们体内的病毒为了躲过免疫系统的攻击，必须通过变异使自己的活力减弱，这样其宿主就更容易控制它们。
这项研究是理论数字处理和真正实验之间的一个有趣的碰撞。“我们在这篇文章中表现出来的东西是理论性的，”沃克说，“但是这个结果又会进一步在人类数据库中得到证实。”
这个小组认为这可使其他人发展出类似的防御机制。我们需要先将其免疫系统暴露于模拟Gag蛋白(包括属于扇区3的区域)的蛋白片段中，他们的免疫系统会对这些蛋白形成记忆，然后感染HIV时，它们就能直接攻击病毒的薄弱部位。沃克说：“我们现在需要用这种新技术作出免疫原，来观察是否能克服目前研制HIV疫苗所面对的主要阻碍，即病毒多样性和病毒进化出逃避免疫应答的能力。”
目前越来越多的科学家试图通过研究病毒如何进化及研究病毒的突变群体，来控制病毒。例如，宾夕法尼亚大学约书亚•普洛特金(Joshua Plotkin)的团队正在寻找接连发生的突变，来预测流感病毒的进化。这些突变能互补或增强对方的效果，突变的总效果比它们各自的效果叠加之和要多，普洛特金正试着用这一性质来确定预示着严重变异的那些无害变异。
普洛特金对戴希瑞尔的研究很感兴趣。他说：“这篇文章，以及近年来其他的几篇文章，说明了控制进化的规则，尤其是对细菌和病毒进化规则的译解，具有实际价值。”
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| 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 |
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New hope for AIDS vaccine
2011-06-28 Author: Source Network Nutshell: MSN Digital IT Zebian: Wang Hao
"HIV discovery allows us to develop a future vaccine against AIDS ... we hope to have available within about two years to test AIDS vaccine." - Margaret • Hechler (Margaret Heckler), U.S. Department of Health and Minister of Public Service, April 23, 1984.
27 years later, and now people are still not developed an AIDS vaccine. The reason is simple, HIV evolved too quickly. HIV can produce every day about 100 billion new virus particles, and this process is very inaccurate. Most of the replication of genetic material has high accuracy, but the HIV replication process in a large number of errors occur, resulting in a group of individual variation, result in any drug or vaccine for HIV will soon fail.
To deal with this changing opponents, some scientists dedicated to finding HIV proteins has remained the same part. These "conserved regions" in a sense is very important, if they mutate, virus replication will be reduced. If training the immune system to attack these areas, then the virus can either die or become weak.
But the virus still a third option, which can modify other parts of its own protein, resulting in a conservative area is no longer important, so that it can escape the immune system's defenses, rather than their own will cause any damage. HIV has once again escaped.
From the Massachusetts Institute of Technology Vincent • Daixiruier (Vincent Dhairel) and Ka Xike • Xie plus (Karthik Shekhar) that we need a new approach. • chakra a birdie by the Arup (Arup Chakraborty) and Bruce • Walker (Bruce Walker) led study identifies many of the HIV protein conserved region, which they called "HIV sector", in other viruses Regional changes all of these areas still remain unchanged. HIV to evade the immune system to attack all these areas, we must generate many different variations, which would certainly weaken the vitality of it.
This is a novel approach. "It is the field of HIV research has injected fresh blood." Walker said, he was found almost from HIV has been studying it since. "We discussed the challenges in this field, chakra birdie that our understanding of HIV evolution is too narrow, and proposed this method."
Daixiruier and Xie added using a technique called "random matrix theory" technology to identify these conserved regions. This technique can detect changes in a manner consistent with the target group that originally came from high-energy physics, it was also used in economics to study the stock price volatility. The team used the technical analysis from a large database of patients with HIV protein sequences. "Random matrix theory analysis of a stock so that people can share any contact with the other." Walker said, "We use the same approach to analyze the evolution of a region and other regions are associated with the evolution, the result is there."
They analyzed the composition of the HIV Gag protein capsid, the protein embedded in the surface of the virus, the immune system targets. Daixiruier and thank increase Gag protein identified in the five sectors, each sector includes co-evolution of the region, and in these areas, rarely mutate.
In these sectors, the sector 3 is more special, it will be different for Gag protein combination play an important role. Without them, the virus can not assemble their capsid. If there is a change in the region, the virus can deal with, but if there are several changes in the region, will be exposed to the virus, and decreased activity.
Daixiruier and Xie added a corollary if the immune system to target several areas of sector 3, HIV would be difficult to evolve, that is, try pressing the virus to evolve to deal with a terminal evolution of the virus too quickly. In fact, in reality some people have done this.
Infected with HIV every three hundred people, about one person's life will not get AIDS, these people life can coexist with the virus, but not develop the disease. Daixiruier and Xie added that their immune cells targeting the sector part 3 Gag protein. This helps to explain what makes them so special. The virus in their bodies to escape the immune system attack, must make their own energy through reduced variability, so that its easier to control their hosts.
This study is the theory test between digital processing and a real interesting collision. "We have shown in this article is a theoretical thing," Walker said, "but the result will be further confirmed in the human database."
The Panel considers that this will enable others to develop a similar defense mechanism. We need first exposed to the immune system simulation Gag protein (belonging to sectors including the area 3) of the protein fragments, their immune system will form a memory of these proteins, and then infected with HIV, they will be able to directly attack the virus is weak parts. Walker said: "We now need to use this new technology to make the immunogen, to see whether the current development of HIV vaccines overcome the main obstacle faced by that virus diversity and evolution of the virus to evade immune responses."
More and more scientists try to study how viruses evolve through mutation of the virus and study groups, to control the virus. For example, the University of Pennsylvania • Plotkin Joshua (Joshua Plotkin) team is looking for a series of mutations, to predict the evolution of influenza viruses. These mutations can complement or enhance each other's effects, the total effect of mutations than the effect of superposition of their individual and to many, Plotkin Kim try to determine the nature of the mutation indicates that serious harm to those variations.
Plotkin's study of Daixiruier interested. He said: "This article and other articles in recent years, indicating that control the evolution of rules, especially for bacteria and viruses to decipher the rules of evolution, has real value."
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