a dynamic landscape for antibody binding modulates antibody-mediated neutralization of west nile virus一个动态的景观为调节抗体介入西尼罗河病毒的中和抗体绑定.pdfVIP

A Dynamic Landscape for Antibody Binding Modulates Antibody-Mediated Neutralization of West Nile Virus 1. 1. 2 3 Kimberly A. Dowd , Christiane A. Jost , Anna P. Durbin , Stephen S. Whitehead , Theodore C. Pierson1* 1Viral Pathogenesis Section, Laboratory of Viral Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America, 3 Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America Abstract Neutralizing antibodies are a significant component of the host’s protective response against flavivirus infection. Neutralization of flaviviruses occurs when individual virions are engaged by antibodies with a stoichiometry that exceeds a required threshold. From this ‘‘multiple-hit’’ perspective, the neutralizing activity of antibodies is governed by the affinity with which it binds its epitope and the number of times this determinant is displayed on the surface of the virion. In this study, we investigated time-dependent changes in the fate of West Nile virus (WNV) decorated with antibody in solution. Experiments with the well-characterized neutralizing monoclonal antibody (MAb) E16 revealed a significant increase in neutralization activity over time that could not be explained by the kinetics of antibody binding, virion aggregation, or the action of complement. Additional kinetic experiments using the fusion-loop specific MAb E53, which has limited neutralizing activity because it recognizes a relatively inaccessi