Two NC State scientists using proteomics techniques have discovered a potential deterrent to the epidemic of Dengue Fever—a viral disease delivered by mosquitos to over 100 million people in the Third World and causing 250,000 deaths each year. The disease is second only to malaria among the world's biggest health problems.

Dr. Dennis Brown and Dr. Raquel Hernandez, a husband and wife research team in the Department of Molecular and Structural Biochemistry, made the discovery while looking for something else. Brown and Hernandez have worked for years investigating the structure, function and assembly of the model-membrane containing virus Sindbis, with the goal of producing an image of the virus structure at atomic resolution.

It was a Kodak moment," says Brown. "We were doing experiments to determine a specific virus protein-protein interaction, and Raquel made a mutant that blocked the protein interaction in mammalian cells. We were surprised to find that when the mutant virus was put into insect cells, the alternate host for the virus, it grew at normal levels. We realized immediately that we had identified a protein domain that we could mutate such that it will grow in insects but not in mammals.”

Brown and Hernandez then removed the protein domain from the virus genome using molecular cloning techniques. In preliminary tests in a mouse model system, they found that the mutant is an excellent vaccine. “Using this approach,” Brown says, “it should be possible to make a vaccine against any one of the 600 to 700 viruses that are carried by blood sucking insects.”

Brown and Hernandez received a provisional patent on the discovery in December 2001 and are now in the process of making mutants for some of those other variations that cause diseases such as Dengue 2, Yellow Fever and West Nile Virus. The best-case scenario is now to find a vaccine company to get the cell line certified by the FDA and to produce the vaccine strains in sufficient quantities. "Like many lifesaving vaccines, it would probably not be affordable in Third World countries," Hernandez explains. "Therefore, an organization such as the World Health Organization or the Bill and Linda Gates Foundation would have to get behind the distribution of the vaccine."

Brown agrees, adding: "This is an example of how basic research that had no apparent medical value led to something of tremendous potential benefit to society."

For more information, please visit
biochem.ncsu.edu/faculty/brown/brown.htm