Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes
Localization and characterization of flavivirus envelope glycoprotein cross-reactive epitopes
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DOI：
10.1128/jvi.78.24.13975-13986.2004
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Chang, GJJ
中科院分区：
文献类型：
--
作者：
Crill, WD;Chang, GJJ
黄病毒 E 糖蛋白是诱导保护性免疫的主要抗原，对于膜融合至关重要，并介导与细胞受体的结合。人类黄病毒感染会刺激病毒物种特异性以及黄病毒交叉反应性免疫反应。人类血清中的黄病毒交叉反应抗体给血清诊断带来了严重的问题，特别是对于继发性黄病毒感染，因为很难区分初级和次级交叉反应血清抗体。黄病毒交叉反应性血清抗体亚中和水平的存在可能通过抗体依赖性增强导致继发性黄病毒感染的严重程度急剧增加。因此，了解黄病毒 E-糖蛋白交叉反应表位对于改善公共卫生对这些严重疾病的反应至关重要。我们鉴定了六个 E-糖蛋白残基，它们被整合到三个不同的黄病毒交叉反应表位中。这些被不同单克隆抗体识别的表位中的两个包含位于高度保守的融合肽内的重叠连续残基。第三个表位由不连续残基组成，其结构与登革热病毒血清型 2 E-糖蛋白位置 231 处严格保守的色氨酸相关。
The flavivirus E glycoprotein, the primary antigen that induces protective immunity, is essential for membrane fusion and mediates binding to cellular receptors. Human flavivirus infections stimulate virus species-specific as well as flavivirus cross-reactive immune responses. Flavivirus cross-reactive antibodies in human sera create a serious problem for serodiagnosis, especially for secondary flavivirus infections, due to the difficulty of differentiating primary from secondary cross-reactive serum antibodies. The presence of subneutralizing levels of flavivirus cross-reactive serum antibodies may result in a dramatic increase in the severity of secondary flavivirus infections via antibody-dependent enhancement. An understanding of flavivirus E-glycoprotein cross-reactive epitopes is therefore critical for improving public health responses to these serious diseases. We identified six E-glycoprotein residues that are incorporated into three distinct flavivirus cross-reactive epitopes. Two of these epitopes which are recognized by distinct monoclonal antibodies contain overlapping continuous residues located within the highly conserved fusion peptide. The third epitope consists of discontinuous residues that are structurally related to the strictly conserved tryptophan at dengue virus serotype 2 E-glycoprotein position 231.