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Cryo-EM structure of an antibody that neutralizes dengue virus type 2 by locking E protein dimers
There are four closely-related dengue virus (DENV) serotypes. Infection with one serotype generates antibodies that may cross-react and enhance infection with other serotypes in a secondary infection. We demonstrated that DENV serotype 2 (DENV2)–specific human monoclonal antibody (HMAb) 2D22 is therapeutic in a mouse model of antibody-enhanced severe dengue disease. We determined the cryo–electron microscopy (cryo-EM) structures of HMAb 2D22 complexed with two different DENV2 strains. HMAb 2D22 binds across viral envelope (E) proteins in the dimeric structure, which probably blocks the E protein reorganization required for virus fusion. HMAb 2D22 “locks” two-thirds of or all dimers on the virus surface, depending on the strain, but neutralizes these DENV2 strains with equal potency. The epitope defined by HMAb 2D22 is a potential target for vaccines and therapeutics.
通过锁住E蛋白二聚体的中和登革热病毒2型抗体的冷冻电镜结构
登革热病毒具有4种血清型，彼此间非常相似。 感染一种血清型产生的抗体，在第一次感染中，可以与其他型有交叉反应 且提高感染, 作者揭示了登革热血清二型的人单克隆抗体对一种抗体增强登革热感染的模型鼠具有治疗效果。作者们用冷冻电镜的方法解析了这个人的单抗与两种登革热2型的病毒复合物。
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发表于 2015-7-8 05:44:02
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发表于 2015-7-8 19:23:01
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