The Epsilon 15 virus as seen by the cryo-electron microscope. Graphic courtesy of Nature/Jiang Laboratories
Viruses that were only recently too small to get a good picture of have now been caught in the dead center of a microscope. Detailed pictures of these bugs will allow scientists to become better equipped to wage the war against viral diseases.
Using custom coding and a novel method for freezing samples, Wen Jiang, who recently joined Purdue University's Department of Biological Sciences, developed a procedure to process images so refined they can get a high-resolution, 3D image of internal structures of viruses as small as 9.5 angstroms—less than a billionth of a meter—across. One example is the knob-like tail of the Epsilon 15 virus, a bacteriophage (or phage) that attacks the salmonella bacterium commonly found in uncooked meat and eggs.
"This technique allowed us to see the whole virus instead of just parts of the virus," said Jiang. "From a technical point of view, this will open the door to studying many other viruses."
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Samples are first flash frozen in a liquid to avoid crystallization and to preserve the virus in perfect living condition. Then over 15,000 2D images are taken of the sample, all standard procedure when trying to examine a virus only 700 angstroms wide. The real breakthrough is Jiang's new image processing algorithm, which can interpret the 2D images into a full 3D reconstruction of the virus.
Some of the pictures were so detailed that they showed the virus' coiled up DNA poised to attack a bacterium, researchers say.
Phages, like the Epsilon 15, are viruses that attack bacteria responsible for a number of human diseases. For every bacterium, nature offers several phages that can neutralize it. As bacteria continue to develop immunities to our antibiotics, phages could prove to be a better weapon in the fight against diseases.
"Imagine you have a bacteria infection and you treat it with these phages; these would exclusively attack bacteria rather than human cells," said Juan Phang, a graduate student at Baylor College of Medicine, Jiang's previous employer, who assisted on the project.
In order for the viral treatment to be a reality, scientists will first need to better understand how phages work. This is why Jiang's cryo-electron microscope is so useful.
"Down the line we will be able to visualize the infection process itself, and we'd like to learn something about what's happening at the cell surface when the phage docks, cause those might be sites that can be targeted for drugs," said Peter Weigele, a researcher at MIT who aided Jiang in the research.
Researchers may also be able to use the cryo-electron microscope to study viruses themselves—such as the herpes simplex virus— to further understand how they infect humans.