University of Virginia School of Medicine scientists have unraveled the mystery of a strange virus in the hopes of creating more effective tools in the war against human disease. The secret weapon this virus may offer? "Armor" for disease-fighting DNA courtesy of the SIRV2 virus, who calls acid at almost boiling temperatures home.
"What's interesting and unusual is being able to see how proteins and DNA can be put together in a way that's absolutely stable under the harshest conditions imaginable," says Edward H. Egelman, PhD, of the UVA Department of Biochemistry and Molecular Genetics in a recent press release. "We've discovered what appears to be a basic mechanism of resistance - to heat, to desiccation, to ultraviolet radiation. And knowing that, then, we can go in many different directions, including developing ways to package DNA for gene therapy."
Dressing up DNA for delivery is important because our bodies fight viruses by detecting, degrading, and ousting foreign DNA. This protective mechanism has stumped scientists and doctors hoping to use genes to combat disease. The unusual SIRV2 virus, however, is providing scientists with a pattern for a DNA suit of armor that may be impenetrable.
SIRV2 invades Sulfolobus islandicus, a microscopic organism that thrives in "extremely unusual" conditions: acidic hot springs that run to 175 degrees F and higher-the virus is built for hostile environments.
Egelman and his team discovered that the SIRV2 virus and the spores formed by bacteria to live on in extreme environments like these share some notable similarities. "Some of these spores are responsible for very, very horrific diseases that are hard to treat, like anthrax. So we show in this paper that this virus actually functions in a similar way to some of the proteins present in bacterial spores," he says.
Clostridium difficile, or C. difficile, also forms spores which, according to the Centers for Disease Control and Prevention, present an "urgent" threat level. Given that these tiny germs kill about 30,000 in the US each year within 30 days of diagnosis, this seems apt.
"Understanding how these bacterial spores work gives us potentially new abilities to destroy them," Egelman says. "Having this basic scientific research leads in many, many directions, most of which are impossible to predict, in terms of what the implications are going to be."
What's the secret of success in hostile conditions for the SIRV2 virus? SIRV2 transforms its DNA into the structural state known as A-form. DNA researcher Rosalind Franklin detected this structural state more than 50 years ago.
"This is, I think, going to highlight once again the contributions she made, because many people have felt that this A-form of DNA is only found in the laboratory under very non-biological conditions, when DNA is dehydrated or dry," Egelman says. "Instead, it appears to be a general mechanism in biology for protecting DNA."
