The eerily random path of a virus poised to attack has been caught on video.
Using a new microscopy technique, researchers at Duke University in Durham, North Carolina have visualized a virus bouncing around the intestinal lining, looking for entry into a cell.
To use a home-invasion metaphor, the moment captured on video "would be the part where the burglar has not broken the window yet," Courtney "CJ" Johnson, an associate at the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia, who conducted the research while earning her doctorate at Duke, said in a statement.
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Viruses are everywhere, and the body has evolved a number of barriers to keep them from reaching the insides of cells, where viruses can use the cellular machinery to create more copies of themselves, sparking an infection. In the intestines, a layer of protective, mucus-secreting cells keep viruses at bay, but these defenses sometimes fail.
"How do viruses navigate these complex barriers?" Kevin Welsher, an assistant professor of chemistry at Duke who co-authored the research, said in the statement.
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Peering into this process is no simple matter. Viruses are hundreds of times smaller than cells, making imaging both at the same time very difficult — like taking a picture of a complete skyscraper and a person standing in front of it at the same time, Johnson said. Viruses also move very rapidly when they're outside of cells.
To overcome these issues, the researchers developed a new method that combines two microscopes. First, they "tag" a virus with a fluorescent chemical compound. A tracking microscope then sweeps a laser across the tagged virus order to update the position of the virus every millionth of a second. This all happens on a moving platform so that the microscope can keep the virus in focus.
Meanwhile, the second microscope takes three-dimensional images of the cells around the virus. This microscope also uses lasers to keep the background image from blurring as the microscopic platform shifts around.
The virus in the video is not a natural virus, but a non-infectious lentivirus — a genus of retroviruses with long incubation periods — wearing the exterior of a vesicular stomatitis virus. A real vesicular stomatitis virus causes mild fevers in humans and other animals.
The video shows the virus skimming randomly over the surface of the surrounding cells. It occasionally bumps into a welcoming receptor and binds to the cell surface, but this doesn't immediately indicate that an infection is afoot; often, the virus detaches and bounces away.
So far, the researchers can only track a viral particle for a few minutes before the fluorescent compound wears away and the particle goes invisible. It will take a tracking time of tens of minutes to follow a virus through the entire process of skimming, binding, and infecting a cell, the researchers reported Nov. 10 in the journal Nature Methods. The researchers are working to develop brighter, longer-lasting tracking compounds so that they can image viruses in increasingly more realistic cellular environments over longer periods of time.
"This is the real promise of this method," Welsher said. "We think that's something we have the possibility to do now."
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