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.

中文翻译：

---

抗体介导的中和和增强西尼罗河病毒感染的化学计量学。

抗体与黄病毒表面包膜蛋白的二十面体排列结合可导致中和或增强感染。我们评估了有多少抗体必须与西尼罗河病毒 (WNV) 上的给定表位结合才能实现中和。最有效的单克隆抗体 (mAb) 在导致病毒粒子上可及位点占用率低的浓度下阻断感染，当 180 种包膜蛋白中只有 30 种被结合时，就会发生中和作用。相比之下，弱中和 mAb 识别病毒体上的位点较少，需要几乎完全占据来抑制 WNV 感染。对于所有研究的 mAb，当与病毒体对接的 mAb 数量不足以中和时，可能会增强带有激活 Fc-γ 受体的细胞的感染。因此，