Cryo-electron microscope image of T4 viruses
image: Michael Rossmann & collaborators
This is an artist's rendition of a T4 virus infecting a bacteria cell.
image: Michael Rossmann and collaborators
How Viruses Attack
As the days get warmer we swap flu season for West Nile. But whatever the virus, they all do their harm by infecting cells. Now high-resolution images have revealed in stunning detail how one virus does it. This ScienCentral News video has more.
A Picture is Worth a Thousand Words
Looking like something out of a science fiction movie, a remarkable animation created by researchers at Purdue University, in collaboration with the Institute of Bioorganic Chemistry in Moscow and The Tokyo Institute of Technology, illustrates a virus ten thousand times smaller than the head of a pin infecting a living cell.
Structural biologist Michael Rossmann, Purdue's Hanley Distinguished Professor of Biological Sciences, and his colleagues, created the animation based on actual, never before seen, high-resolution images they captured of the virus. The new understanding they have gained about how viruses infect other cells could help science fight viral diseases and deadly bacterial infections, or potentially one day be harnessed for medical benefit.
Combining two different imaging techniques, crystallography and cryoelectron microscopy, Rossmann and his team took thousands of pictures of a virus called T4 as it infected E. coli bacteria, a variety of which is commonly associated with food poisoning. "The crystallography technique is able to obtain the structure of individual proteins at an atomic resolution where we can see individual atoms and see their relationship to each other," Rossmann explains. "The electron microscopy enables us to look at larger units such as the whole virus."
The high-resolution images came from their effort to understand, in new detail, the intricate workings of how these cell-killing machines wreak their havoc. "Many viruseseven most viruseswill use the same kind of mechanism by which they infect cells," Rossmann explains. "By looking at T4, looking at these details, we are therefore able to tell quite a bit about how many viruses infect cells."
They found that the 'docking bay' or baseplate of T4, which latches onto the surface of other cells, changes shape. The proteins that form the normally hexagonal, honeycomb-shaped baseplate rearrange themselves, causing it to open in to a star shape. This enables the virus to infect the E. coli by piercing its outer surface and injecting its DNA into the cell. "The proteins kind of slither and slide across each other in undergoing very large structural changes," Rossmann says.
Back to Basics
Interested, basically, in understanding how nature works, the group's research is a step forward in fundamental scientific knowledge. Viruses are among the tiniest of biological entities, yet nature has designed them to perform very complicated tasksunderstanding their behavior will open doors for scientists in many disciplines. Rossmann likens their work to looking under the hood of a car in order to understand what makes it run. "That's really what we're doing, we're opening the hood and seeing inside how these biological systems work and understand what they do," he says.
Understanding how T4 infects cells will help science and medicine to fight diseases around the world. The virus could also be used as a nano-sized DNA injection machine, delivering healthy DNA into cells whose genetic material has been damaged by injury or disease. This so-called gene therapy is being developed more and more to prevent and treat genetically-based diseases, such as Parkinson's disease and Alzheimer's disease, where parts of the DNA in the cells of the patient are not functioning properly. "In knowing how T4 injects its genomic material into a cell, we might be able to adapt T4 to target human cells," Rossmann explains. "So you've now got a virus which can target a specific cell and introduce a specific gene into the cell which it requires." Gene therapy using T4 remains a distant possibility.
Through his ongoing work with T4, Rossmann hopes to learn more about the proteins that make up the T4 baseplate, as well was studying the infection process in other viruses. Along with T4, Rossmann and his international team of researchers have increased scientists' understanding of many other viruses, including those that cause Dengue fever, West Nile and the common cold.
Rossmann's research appeared in the August 20, 2004 issue of Cell, and was funded by the National Science Foundation, the International Human Frontier Science Program and the Howard Hughes Medical Institute.
病毒是如何入侵细胞的呢？美国ScienCentral网4月26日报道了来自美国普渡大学、墨西哥生物有机化学研究院、和东京工业大学、的研究人员利用高分辨解析影像逼真地展示了病毒感染活体细胞的全过程。
美国著名生物学家Michael Rossmann及其同事们创制出了真实的、前所未见的病毒影像。这一新成果将在打击病毒和致命性细菌感染方面具有重大意义，而且极有可能应用于医学领域。
研究小组将晶体照像术（crystallography）与冷冻电子显微镜术cryoelectron microscopy结合起来，拍摄了数千张T4病毒感染E. coli细菌时的照片，而且很多都与食物中毒相关。Rossmann解释说：“利用晶体照像术可以在原子级分辨率层面获得单个蛋白质的结构及单个原子之间的关系，而冷冻电子显微镜术能让我们看到整个病毒。”
研究人员利用高分辨解析影像详细地观测到病毒侵袭细胞的复杂过程。大部分病毒感染细胞的机制相同，因此通过观察T4病毒就能掌握基本情况。他们发现T4病毒的中基底板（baseplate）会改变形状，从六边形的蜂窝状变成星形。这样就使得病毒能刺穿E. coli细菌的外表面，并将其DNA注入细胞内。
病毒是大自然中一种极微小的实体，但能够完成非常复杂的程序。因此，掌握了病毒的行为，也就是向基础科学知识的研究前进了一步。
掌握T4病毒如何感染细胞的过程，可以协助全球科学和医学界更好地与疾病作斗争。病毒还可以被用作纳米大小的DNA注射器，将健康的DNA注入遗传物质受损的细胞内。这一技术被称为基因疗法（genetherapy），正在被越来越广泛地用于预防和治疗遗传类疾病，如帕金森和老年痴呆症，这些患者体内细胞的DNA无法正常工作。但将T4病毒用于基因治疗的可能性仍然十分遥远。
Rossmann希望在研究过程中能更深入地了解组成T4病毒中基地板的蛋白质，同时研究其他病毒的感染过程。通过对T4病毒的研究，Rossmann和他的研究小组已经对其他种类的病毒有了更多的了解，包括引起登革热（Dengue fever）、西尼禄（West Nile）和感冒的病毒。
这项研究得到了美国国家自然科学基金会、国际人类前沿科学计划和霍华德休斯医学研究所的资助。
