Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein
Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein
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DOI：
10.1128/jvi.79.2.1223-1231.2005
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发表时间：
2005-01-01
影响因子：
5.4
通讯作者：
Harrison, SC
中科院分区：
文献类型：
--
作者：
Modis, Y;Ogata, S;Harrison, SC
登革热病毒是一种新出现的全球健康威胁。主要的包膜糖蛋白E通过膜融合介导病毒附着和进入。结合但不能中和非同源血清型的抗体增强感染。我们已经确定了晶体结构的可溶性片段的包膜糖蛋白E从登革病毒3型。结构非常类似于登革热2型和蜱传脑炎病毒的E蛋白。登革病毒E蛋白中血清型特异性中和逃逸突变体均位于结构域III的表面上，该结构域III与受体结合有关。虽然针对结构域I中表位的抗体在登革病毒中是非中和性的，但存在识别结构域II中的表位的中和性抗体。这些抗体的中和机制可能是抑制膜融合。我们的结构表明，病毒表面上的相邻聚糖间隔足够宽（至少32埃），它们可以与寡聚凝集素（如DC-SIGN）上的多个碳水化合物识别结构域相互作用，确保对这些推定受体的最大亲和力。
Dengue virus is an emerging global health threat. The major envelope glycoprotein, E, mediates viral attachment and entry by membrane fusion. Antibodies that bind but fail to neutralize noncognate serotypes enhance infection. We have determined the crystal structure of a soluble fragment of the envelope glycoprotein E from dengue virus type 3. The structure closely resembles those of E proteins from dengue type 2 and tick-borne encephalitis viruses. Serotype-specific neutralization escape mutants in dengue virus E proteins are ail located on a surface of domain III, which has been implicated in receptor binding. While antibodies against epitopes in domain I are nonneutralizing in dengue virus, there are neutralizing antibodies that recognize serotype-conserved epitopes in domain II. The mechanism of neutralization for these antibodies is probably inhibition of membrane fusion. Our structure shows that neighboring glycans on the viral surface are spaced widely enough (at least 32 Angstrom) that they can interact with multiple carbohydrate recognition domains on oligomeric lectins such as DC-SIGN, ensuring maximum affinity for these putative receptors.