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.
病毒是如何入侵細(xì)胞的呢,？美國ScienCentral網(wǎng)4月26日報(bào)道了來自美國普渡大學(xué),、墨西哥生物有機(jī)化學(xué)研究院、和東京工業(yè)大學(xué),、的研究人員利用高分辨解析影像逼真地展示了病毒感染活體細(xì)胞的全過程,。
美國著名生物學(xué)家Michael Rossmann及其同事們創(chuàng)制出了真實(shí)的、前所未見的病毒影像,。這一新成果將在打擊病毒和致命性細(xì)菌感染方面具有重大意義,，而且極有可能應(yīng)用于醫(yī)學(xué)領(lǐng)域。
研究小組將晶體照像術(shù)（crystallography）與冷凍電子顯微鏡術(shù)cryoelectron microscopy結(jié)合起來,，拍攝了數(shù)千張T4病毒感染E. coli細(xì)菌時(shí)的照片,，而且很多都與食物中毒相關(guān),。Rossmann解釋說：“利用晶體照像術(shù)可以在原子級分辨率層面獲得單個(gè)蛋白質(zhì)的結(jié)構(gòu)及單個(gè)原子之間的關(guān)系，而冷凍電子顯微鏡術(shù)能讓我們看到整個(gè)病毒,。”
研究人員利用高分辨解析影像詳細(xì)地觀測到病毒侵襲細(xì)胞的復(fù)雜過程,。大部分病毒感染細(xì)胞的機(jī)制相同，因此通過觀察T4病毒就能掌握基本情況,。他們發(fā)現(xiàn)T4病毒的中基底板（baseplate）會改變形狀,，從六邊形的蜂窩狀變成星形。這樣就使得病毒能刺穿E. coli細(xì)菌的外表面,，并將其DNA注入細(xì)胞內(nèi),。
病毒是大自然中一種極微小的實(shí)體，但能夠完成非常復(fù)雜的程序,。因此,，掌握了病毒的行為，也就是向基礎(chǔ)科學(xué)知識的研究前進(jìn)了一步,。
掌握T4病毒如何感染細(xì)胞的過程,，可以協(xié)助全球科學(xué)和醫(yī)學(xué)界更好地與疾病作斗爭。病毒還可以被用作納米大小的DNA注射器,，將健康的DNA注入遺傳物質(zhì)受損的細(xì)胞內(nèi),。這一技術(shù)被稱為基因療法（genetherapy），正在被越來越廣泛地用于預(yù)防和治療遺傳類疾病,，如帕金森和老年癡呆癥,，這些患者體內(nèi)細(xì)胞的DNA無法正常工作。但將T4病毒用于基因治療的可能性仍然十分遙遠(yuǎn),。
Rossmann希望在研究過程中能更深入地了解組成T4病毒中基地板的蛋白質(zhì),，同時(shí)研究其他病毒的感染過程。通過對T4病毒的研究,，Rossmann和他的研究小組已經(jīng)對其他種類的病毒有了更多的了解,，包括引起登革熱（Dengue fever）,、西尼祿（West Nile）和感冒的病毒,。
這項(xiàng)研究得到了美國國家自然科學(xué)基金會、國際人類前沿科學(xué)計(jì)劃和霍華德休斯醫(yī)學(xué)研究所的資助,。
