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Secrets to antibody's success against West Nile Virus surprise scientists

akes up the exterior of the viral envelope. The envelope of a single viral particle or virion is comprised of 180 copies of this protein.

For the new study, scientists determined the detailed structure of a single antibody bound to its envelope protein target region using the technique of protein crystallography. Scientists were able to affirm in greater detail earlier observations suggesting that the antibody will be therapeutic for all strains of West Nile Virus.

Based on this data, they predicted how multiple copies of the successful antibody would bind to a virion.

"We were startled to find that the antibody only seemed to be able to attach to 120 of the 180 copies of the target region in the complete viral envelope," says Grant Nybakken, a Washington University M.D./Ph.D. student who was lead author of the study.

Further tests showed that virions covered in infection-stopping antibodies could still bind to host cells, while antibodies that were less effective at stopping infection could more effectively prevent the virion from binding to host cells.

How does an antibody that's better at preventing the virus from binding to host cells actually turn out to be worse at treating infection? The key may lie in a theory known as antibody-dependent enhancement (ADE) of infection, which has been observed in test tube studies of dengue virus and may be important to the onset of dengue hemorrhagic fever.

This theory suggests that dengue and other viruses may have developed tricks that let them reproduce inside macrophages, the immune cells that normally consume and destroy any object that they find covered in antibodies. In effect, these tricks turn antibodies that should be death warrants into passes into cells where invaders can reproduce.

Fremont cautions that this phenomenon has not been seen in West Nile virus, but notes that when he and his colleagues tested the ability of several antibodies to pr
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Source:Washington University School of Medicine


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