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Ebola Outbreak 2014 2015 by Dr. Fauci


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Antibody Locks Up West Nile Virus Cell-Entry Mechanism

Researchers identified a monoclonal antibody (MAB) that neutralizes West Nile virus (WNV) by binding and crosslinking viral surface proteins that are needed to infect host cells. "The antibody crosslinking causes the virus to become rigid, and this rigidity prevents conformational changes and locks up the infectious mechanism," says Michael Rossmann, study leader at Purdue University in West Lafayette, Ind. Learning how antibodies neutralize this virus could prove important for developing vaccines against infections caused by this mosquito- borne virus or those caused by other flaviviruses.

The WNV surface carries 180 closely packed copies of the envelope, or E, protein within the viral lipid membrane. This protein, the main WNV antigen to which infected individuals produce antibodies, forms dimers that, in turn, bind one another, forming herringbone-patterned complexes, called rafts, that float in the viral membrane.

Among the large numbers of antibodies that are generated in a polyclonal host response to WNV infections, "we're trying to identify which are the most important classes," says Michael Diamond of Washington University School of Medicine in St. Louis, Mo. As part of that search, he recovered CR4354, a human MAB, from a collection of antibodies from patients who recovered from WNV infections. CR4354 stands out because it has strong neutralizing activity, protects mice from WNV, and binds to multiple E proteins on the viral surface.

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