[英语，研究]干扰素如何对抗病毒

StephenW

http://esciencenews.com/articles/2011/04/10/big.picture.how.interferon.induced.genes.launch.antiviral.defenses.revealed
Big picture of how interferon-induced genes launch antiviral defenses revealed
Published: Sunday, April 10, 2011 - 12:33 in Health & Medicine
      When viruses attack, one molecule more than any other fights back. Interferon triggers the activation of more than 350 genes, and despite the obvious connection, the vast majority have never been tested for antiviral properties. A team of researchers, led by scientists from Rockefeller University, for the first time has carried out a comprehensive, systematic evaluation of the antiviral activity of interferon-induced factors. The findings, published online today in the journal Nature, are a first step toward unraveling how these naturally occurring molecules work to inhibit viruses. "We hope this study will open the door to future work on the mechanisms of antiviral molecules," says first author John Schoggins, a postdoctoral associate in Charles M. Rice's Laboratory of Virology and Infectious Disease at Rockefeller. "Such mechanistic studies may set the stage for the development of new and much needed drugs to combat a diverse array of viruses that pose significant health threats to people worldwide."
The researchers were interested in type I interferon, a cellular molecule that is made when a person becomes infected with certain viruses. Type I Interferon is used clinically in the treatment of some viral diseases, such as hepatitis C, and its presence has been shown to significantly limit the severity of certain viral infections.
Schoggins and his colleagues, including researchers from the Aaron Diamond AIDS Research Center and the Howard Hughes Medical Institute, systematically evaluated the majority of common interferon-induced genes, one by one, to determine which of them had antiviral activity against a panel of disease-causing viruses, including the hepatitis C virus, HIV, West Nile virus, the yellow fever virus and chikungunya virus.
The scientists used a cell-based "screen" to measure the ability of each gene to halt the growth of the viruses: One by one, genes were delivered into the cells that were then infected with virus. In cells that had no interferon-induced genes delivered, Schoggins and his team observed normal levels of virus replication. In cells that had interferon-induced genes delivered, they occasionally found "hits" that could significantly impair virus replication.
Overall, Schoggins and his colleagues found that each virus tested was susceptible to inhibition by a unique subset of these interferon-induced genes, with some genes having specific effects on only one virus, and other genes having more broad effects on multiple viruses.
The researchers also showed that two genes in combination were more potent than either gene alone, supporting the long-standing hypothesis that many interferon-induced factors work in a combinatorial fashion. A number of the factors, the researchers found, work by interfering with the process by which viral RNA is translated in protein.
"It's fascinating that evolution has provided us with an array of hundreds of molecules that can be summoned by the host upon viral infection," says Schoggins. "Even more interesting is that none of these factors on their own are 'magic bullets' that can eradicate the virus. Instead, the cell relies on the cooperative action of numerous factors to effectively shut down the virus."
Schoggins and his colleagues hope their work will ultimately help inform the design of new antiviral drugs.
"This study is a first step toward unraveling how these previously uncharacterized, naturally occurring interferon-induced factors inhibit viruses," says Rice, who is the Maurice R. and Corinne P. Greenberg Professor at Rockefeller and scientific director of the Center for the Study of Hepatitis C. "In future studies, we hope to reveal the exact mechanisms by which these molecules suppress viral replication. If this can be done, then we will have a platform for the development of novel drugs that may be beneficial for combating viral infections."
  Source: Rockefeller University



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StephenW

干扰素

诱导的基因启动如
何防御抗病毒
发布时间：星期日，2011年4月10日 - 健康与医学12:33

当病毒攻击, 一个分子,干扰素,比任何其分子,还击 。干扰素触发了350多基因的激活，尽管有明显的方面，绝大多数从未针对抗病毒特性进行测试。一个研究小组由来自洛克菲勒大学的科学家领导的第一次，已经进行了全面，干扰素的诱导因素，抗病毒活性的系统评价。这项研究结果发表在自然杂志网络版上，是实现第一步，如何解开这些自然发生的分子工作，抑制病毒。 “我们希望这项研究将打开大门，对抗病毒药物的分子机制今后的工作，说：”约翰Schoggins第一作者，在查尔斯M. Rice的病毒学与传染病实验室的博士后副洛克菲勒。 “这样的机理研究可能为新的和急需的药品发展的阶段，打击了病毒的健康构成重大威胁全世界人民多样化。”

研究人员感兴趣的是I型干扰素，是一种细胞的分子，当一个人变得作出一定的病毒感染。 I型干扰素是临床上使用的一些病毒疾病，如丙型肝炎，治疗，并已被证明它的存在大大限制某些病毒感染的严重性。

Schoggins和他的同事们，包括来自艾伦戴蒙德艾滋病研究中心和霍华德休斯医学研究所的研究人员，系统地评价了普通干扰素诱导的大多数基因，一个接一个，以确定哪些对他们有一个小组的抗病毒活性的疾病，导致病毒，包括丙型肝炎病毒，艾滋病毒，西尼罗河病毒，黄热病病毒，基孔肯雅病毒。

科学家们使用细胞为基础的“屏幕”来衡量每一个基因的能力，以制止病毒的增长：一个接一个，把该基因，然后与病毒感染的细胞传递。在没有细胞干扰素诱导的基因传递，Schoggins和他的团队观察到的病毒复制正常水平。干扰素在细胞有诱导基因的传递，他们偶然发现“点击”，可以大大削弱病毒的复制。

总体而言，Schoggins和他的同事发现，每一种病毒测试是由这些干扰素诱导独特的基因子集，容易与某些基因有抑制上只有一个病毒的具体影响，以及其他多种病毒的基因上更具有广泛的影响。

研究人员还发现，两个基因的组合更强大的比任何单独的基因，支持长期的假设，许多干扰素诱导的因素组合的方式工作。一个数的因素，研究人员发现，通过与病毒RNA，其中的蛋白质翻译过程干预工作。

“这是迷人的，进化提供了一种分子可以被病毒感染宿主后召集数百数组我们，说：”Schoggins。 “更有意思的是，这些因素都对自己是'魔术子弹'，可以消除病毒。相反，细胞上的许多因素，有效地关闭该病毒依赖的合作行动。”

Schoggins和他的同事们希望他们的工作最终会帮助通知新的抗病毒药物的设计。

“这项研究是朝着解开这些以前未知功能如何，自然发生的干扰素诱发因素抑制病毒的第一步，”赖斯说，谁是莫里斯格林伯格R.和科琳娜教授洛克菲勒和科学的研究中心主任对丙型肝炎“在未来的研究，我们希望能准确揭示了这些分子机制，抑制病毒复制。如果可以做到这一点，那么我们将有一个发展的新型药物，可​​能用于防治病毒感染的有益平台“。
资料来源：美国洛克菲勒大学