The Journal of Young Investigators: An Undergraduate, Peer-Reviewed Science Journal

18 September 2006 - Movies and novels abound with stories of previously harmless viruses that suddenly mutate into an epidemic-level killer strain, but these fictional accounts rarely explain how their imagined disasters come about. In reality, University of Florida researchers have discovered one way such a dangerous mutation could happen - viruses changing how they attach to cells. Their paper in the current issue of the Journal of Biological Chemistry suggests that viruses, which attach to carbohydrates protruding from the cell wall, can switch which carbohydrates they bind, allowing them to infect a cell more efficiently.

Researchers first realized that viruses could mutate in this manner while studying the Minute Virus of Mice. One strain, MVMi, can cause fatal hemorrhaging in mice, while the MVMp strain is generally harmless. However, a few years ago, the MVMp strain began harming mice as well, after a mutation that altered only one or two amino acids, or building blocks of the virus’s outer protein shell.

To see how a small mutation could have a dramatic effect, researchers used a new technique called a glycan array, where viruses are exposed to a plate covered in different carbohydrates, or glycans. When the viruses bind to carbohydrates in the test, it also indicates which carbohydrates a virus attaches to in cell walls. Upon running the array, they found that in addition to the carbohydrates bound by the normal MVMp strain, the mutant strains also bound a carbohydrate to which the MVMi strain attaches.

"A single amino-acid change in the virus' protein shell changes how it can grip the cell, making it more deadly," said author Mavis Agbandje-McKenna. "Actually, the affinity is reduced, so the more deadly strain of the virus does not bind as tightly. We're not sure why, but it may be because it can more easily let go and get into the cell to cause disease.”

The researchers speculated that this would allow the virus to infect the cell before the body’s immune system had time to respond. This understanding of one way in which viruses mutate opens the door to future research in human medicine. First, it offers an understanding of how epidemic-causing strains could develop.

"If you think about the flu virus, a few simple amino acid changes can be the difference between a virus your body can defend against and one that will make you sick," said Agbandje-McKenna.

In addition, a thorough understanding of how viruses identify and infect specific cells could allow for the development of targeted gene therapies or specific treatment of cancer.

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