| Literature DB >> 18005691 |
Theodore C Pierson1, Qing Xu, Steevenson Nelson, Theodore Oliphant, Grant E Nybakken, Daved H Fremont, Michael S Diamond.
Abstract
Antibody binding to the icosahedral arrangement of envelope proteins on the surface of flaviviruses can result in neutralization or enhancement of infection. We evaluated how many antibodies must bind to a given epitope on West Nile virus (WNV) to achieve neutralization. The most potent monoclonal antibodies (mAbs) block infection at concentrations that result in low occupancy of accessible sites on the virion, with neutralization occurring when as few as 30 of 180 envelope proteins are bound. In contrast, weakly neutralizing mAbs recognize fewer sites on the virion and require almost complete occupancy to inhibit WNV infection. For all mAbs studied, enhancement of infection is possible in cells bearing activating Fc-gamma receptors when the number of mAbs docked to the virion is not sufficient for neutralization. Thus, neutralization is best described by a model requiring "multiple hits" with the cumulative functional outcome determined by interplay between antibody affinity and epitope accessibility.Entities:
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Year: 2007 PMID： 18005691 PMCID： PMC2656919 DOI： 10.1016/j.chom.2007.03.002
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023