Sunday, September 19, 2004
Catching a Virus in the Act
By Kristen Philipkoski Also by this reporter Page 1 of 1
02:00 AM Sep. 18, 2004 PT
Scientists can see how a virus causes infection by interacting with DNA, thanks to the first molecular-scale images of the phenomenon. Now that they can see how the virus does its dirty work, researchers can try to build a drug to block it.
Biologists from Brookhaven National Laboratory and Albert Einstein College of Medicine created a computer model of DNA binding to an adenovirus enzyme at a point in time they believe is critical for causing infection. The image they generated appears on the October 2004 cover of Molecular and Cellular Proteomics.
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Adenoviruses cause respiratory, gastrointestinal and eye infections, including pink eye. Some adenovirus eye infections lead to blindness and, in people whose immune systems are challenged, the virus can be deadly.
When the researchers caught a glimpse of the virus in action, they saw for the first time that DNA bound directly to the virus enzyme, called a protease. The researchers believe the protease uses the DNA as a guide to spread infection.
"This was the first example of that ever happening, and a lot of people didn't believe this when we first published it," said Walter Mangel, a co-author of the paper and head of the lab at Brookhaven that performed the work.
His lab first published data suggesting the phenomenon back in 1993, when it was met with some skepticism. But now they have visual proof.
The team used a technique called synchrotron footprinting, a technology pioneered by another study co-author, Mark Chance at the Albert Einstein College of Medicine. Synchotron footprinting involves bombarding biological molecules with X-rays to create an image of their surface.
Before performing the synchotron footprinting, the researchers crystallized the adenovirus enzyme. In crystal form, X-rays bounce off of the enzyme, and by measuring the reflected X-rays, the scientists can determine the exact location of each atom.
Sayan Gupta, a researcher at Einstein College of Medicine and the study's lead author, performed the synchotron footprinting on the adenovirus and DNA using the National Synchotron Light Source.
Using data taken from the X-ray bombardment, researchers used specialized software to create a computer model of the enzyme and the DNA.
"We think the protease binds to DNA almost like a train moving along a track," Mangel said.
Because the DNA binding site is long, drugs have lots of space where they could interfere with the DNA and enzyme interaction, Mangel said. He and his colleagues have already started looking for potential drugs and hope within a year to send some for testing to the National Institutes of Health, which funded the study along with the U.S. Department of Energy.
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