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Virus Can Mutate lethally With Help Of Carbohydrates

Study finds that viruses too look out for carbohydrate molecules so as to prepare for an invasion onto our cells.//

A new study by the University of Florida, which has been published in the current Journal of Biological Chemistry, states that it not only humans but viruses too that crave for carbohydrates. The researchers have stated that the viruses hang on to the carbohydrates that overhang from the surface of our cells and stage an invasion in the body.

The researchers explained that the viruses on changing the carbohydrates they attach to are able to infect cells more efficiently. This finding the researchers hope would prove to be valuable to scientists for finding ways to fight cancer or brain diseases. The discovery they hope would also explain how flu and other viruses are always to stay a step ahead of our body's own resourceful immune system.

Mavis Agbandje-McKenna, Ph.D., an associate professor of biochemistry and molecular biology in the UF College of Medicine and senior author of the paper said, “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. It seems structural juxtapositions of amino acids play a role in determining how viruses recognize cells and whether the viruses are harmful.”

The researchers from the UF came across the opinion of the proteins on the outer shell of the virus mutating to get a more lethal grip on a cell's sugary coat of carbohydrates, or glycans, as they were studying the Minute Virus of Mice, or MVM. They found that that a single strain of the virus, MVMp is actually a harmless strain that causes no ill-effects even in mice that have no functional immune system, but a different version of virus MVMi on the contrary is quite fatal to the mice.

The researchers found that both viruses resemble a miniature, 20-sided soccer balls, and between them their outer protein shells were different by only 14 out of more than 500 amino acids. They also found that a couple of years back these normally mild MVMp viruses mutated quite suddenly and became harmful to the defenseless mice.

Agbandje-McKenna, who is associated with both UF's McKnight Brain Institute and the UF Genetic Institute explained “One or two changes in amino acids made the difference between a virus that kills and one that does not kill mice. We wanted to know how such a slight change could make this virus become lethal.” An international team of more than 230 scientists under the National Institute of General Medical Sciences, the UF researchers working with the Consortium for Functional Glycomics, had become the first to use a new technique called a glycans array to study how a whole, intact virus interacts with carbohydrates.

The scientist’s explained to have exposed 189 glycans that were mounted on a 3-by- 5-inch plastic plate to dangerous MVMi, harmless MVMp and three potentially dangerous, mutant strains of MVMp. They claimed to have found that the MVMp proteins stuck to the same three glycans on the plate. However, one of the mutant MVMp viruses also bound to an additional glycan and that one was associated with the more dangerous MVMi strain.

She said, “A single amino-acid change in the virus' protein shell changes how it can grip the cell, making it more deadly. Actually, the affinity is reduced, so the more deadly strain of the virus actually 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. It's not giving the body the time to mount an immune response.” The scientists were of the opinion that on understanding as to how viruses adapt to different hosts and different tissues could be useful for developing gene therapies, which involve introducing specially engineered genes into a patient's cells through the apparently harmless vir uses. It was explained that in cancer treatment, the new genes might be expected to induce the body's natural defenses or actually attack the cancer cells themselves.

According to Hyun-Joo Nam, Ph.D., an assistant scientist in department of biochemistry and molecular biology and the paper's first author, stated that in term of medical treatments, the finding would help in explaining as to why a virus would be able to home in on a cancer or brain cell, by recognizing the sugars on the cell's surface.

Peter Tattersall, Ph.D., a professor of laboratory medicine and genetics at Yale University who was not involved in the research said, “Scientists want to use viruses they know to be nonpathogenic as vehicles for either gene and cancer therapies, and they also want to know how viruses target cancer and other differentiated cells. The most likely medical significance of this finding is for fine-tuning viruses and vectors to target cancer and other differentiated cell types. This is a major field that is advancing rapidly.”



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