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Research pinpoints West Nile virus antibody binding site

West Lafayette, Ind. -- Researchers have learned the precise location where an antibody binds to the West Nile virus, and they have suggested a mechanism for how this antibody neutralizes the virus to prevent infection.

"Science doesn't yet fully understand exactly how neutralizing antibodies work," said Michael Rossmann, the Hanley Distinguished Professor of Biological Sciences in Purdue's College of Science. "This work has shown precisely where the antibody binds to the virus, and we now have a theory for how it interacts with the virus to disarm it. Perhaps we are starting to understand why this particular antibody can inhibit the infectivity of the virus, which is important to understand if a vaccine is going to be developed."

Purdue worked with researchers from the Washington University School of Medicine in St. Louis.

West Nile belongs to a family of viruses known as flaviviruses, which includes a number of dangerous insect-borne disease-causing viruses. The antibody attaches to a protein called an E protein, for envelope protein, which makes up the virus's outer shell. There are 180 copies of E proteins symmetrically arranged in 60 sets of three, forming a geometric shape called an icosahedron, which is made up of triangular facets.

The researchers, however, were surprised to discover that this antibody recognizes only two of the E proteins in each set of three, said Brbel Kaufmann, a postdoctoral research associate working in the Rossmann lab.

"This finding was very unusual," she said. "If the E proteins really are the same, why doesn't the antibody bind to all of the E proteins? This kind of asymmetry, where you have two proteins binding and one not binding, has not been seen before."

The researchers theorize that, although chemically identical, these E proteins exist in different environments relative to each other and might, therefore, have slightly different structures, said Richard J. Kuhn,
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Contact: Emil Venere
venere@purdue.edu
765-494-4709
Purdue University
14-Aug-2006


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