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

Insights may advance vaccines for related viruses including dengue fever. A monoclonal antibody that can effectively treat mice infected with West Nile virus has an intriguing secret: Contrary to scientists' expectations, it does not block the virus's ability to attach to host cells. Instead, the antibody somehow stops the infectious process at a later point.

"This was a complete surprise to us, but it gives us some very useful insights," says senior author Daved Fremont, Ph.D., associate professor of pathology & immunology and of biochemistry & molecular biophysics at Washington University School of Medicine in St. Louis. "Based on what we've learned, we are now developing therapeutic antibodies for related viruses that also are effective at stopping the process of infection after the virus attaches to host cells."

Detailed study of how the antibody physically binds to the virus has provided intriguing clues to how it may block infection. Scientists found evidence suggesting that the antibody prevents the virus from rearranging the protein envelope that surrounds its genetic material after it enters a host cell.

To reproduce, a virus must alter its envelope in order to inject its genetic material inside the cell. After that injection, the virus tricks the host cell into making more copies of the genetic material that can then be assembled into new viral particles or virions and sent out to infect other host cells and reproduce. But with the viral reproduction process blocked by the antibody, scientists suspect that the host cell eventually destroys the virion.

Fremont and colleagues, who publish their results in the Sept. 29 issue of Nature, hope to design a new diagnostic system that can determine whether vaccines for West Nile and related viruses undergoing clinical trials stimulate production of antibodies that stop infections at a similar point.

In 2004, West Nile virus, which is a mosquito-borne flaviviru
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Source:Washington University School of Medicine


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