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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.
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."
Cryo-electron microscope image of T4 viruses image: Michael Rossmann & collaborators
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.
This is an artist's rendition of a T4 virus infecting a bacteria cell. image: Michael Rossmann and collaborators
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.