生物谷报道:现在也许你也像千百万人一样被流感困扰,咳嗽,打喷嚏。病毒通过感染细胞引起普通感冒或埃博拉出血热等疾病。一个科学新闻中心的录像报告展示了病毒感染细胞的详细过程。
一张图片强过千言万语
科学家制作了一张令人惊奇的病毒卡通图片,让人觉得像出自科幻电影。图片展示了比针尖还小一万倍的病毒感染细胞的一瞬间,同时展示了它的结构。图片由一名生物学家及其同事完成。图片是对高倍显微下的真实病毒和对病毒感染细胞的最新的理解。
科学家通过联合使用晶体和低温电子显微成像技术,得到了成千张T4病毒感染大肠杆菌的图片。晶体成像技术可进行原子水平的显像,而低温电子显微技术再使病毒水平成像,二者联合可以同时得到微观和相对整体的图像。了解T4感染大肠杆的机制,有利于了解机制相似的其他病毒感染细胞的过程和机制。
科学家发现,感染发生时T4与细胞表面接触的基板形状改变。其蜂窝状六角形基板打开变成星状,以刺破大肠杆表面,释放DNA进入细胞。可能是蛋白间的滑动造成了这种变形。
回归基础
有趣的是,研究小组发现了解自然的过程就是回归基础科学问题的过程。从理论上了解世界上最小生物体是如何完成复杂任务的,为科学家在许多研究领域打开了视野。
研究T4病毒是如何感染细胞有利于人们对疾病的研究。T4病毒可以作为健康DNA载体系统转染疾病细胞,达到基因治疗的作用。针对帕金森病和老年痴呆病的基因治疗研究正在进行。但真正应用T4病毒作为载体的基因治疗方法还离我们有一段距离。
关于T4病毒的研究还在继续进展中,科学家希望更多的了解构成T4病毒基板的蛋白。通过T4人们对病毒的认识已经提高了很多,包括对西尼罗河,登革热和流感等病毒的认识(http://www.bioon.com/)。
How Viruses Infect
You may be coughing or sneezing out millions of them right now. Viruses, whether the common cold or Ebola, do their harm by infecting cells. As this ScienCentral News video reports, scientists have now shot detailed images revealing how one virus does it.
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 viruses—even most viruses—will 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."
This is an artist's rendition of a T4 virus infecting a bacteria cell.
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 tasks—understanding 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.