Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability.
Measles Virus Hemagglutinin Protein Epitopes: The Basis of Antigenic Stability.
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DOI：
10.3390/v8080216
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发表时间：
2016-08-02
期刊：
影响因子：
--
通讯作者：
Takeda M
中科院分区：
文献类型：
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作者：
Tahara M;Bürckert JP;Kanou K;Maenaka K;Muller CP;Takeda M
使用现有疫苗在全球范围内消灭麻疹在生物学上是可行的，因为麻疹病毒 (MV) 血凝素 (H) 蛋白具有抗原稳定性。 H蛋白负责受体结合，是中和抗体的主要靶标。免疫显性表位，称为血凝表位和套索表位，位于受体结合位点 (RBS) 附近。 RBS 还含有免疫显性表位。受体结合的丧失与靶向 RBS 表位的抗体逃避中和有关。另一个中和表位位于 RBS 附近，在某些基因型菌株中被 N 连接糖屏蔽。然而，无论 N 联糖修饰或这些表位的突变如何，来自疫苗接种者和麻疹患者的人血清以相似的效率中和所有 MV 毒株。另外两个主要表位距离 RBS 较远。一种具有非结构化柔性结构域和线性中和表位。当MV-H形成四聚体（二聚体的二聚体）时，这些表位可能形成二聚体-二聚体界面，并且两个表位之一也可能与F蛋白相互作用。识别这些表位的抗体的中和机制可能涉及抑制 H-F 相互作用或阻断 MV-H 与其受体结合后的融合级联。
Globally eliminating measles using available vaccines is biologically feasible because the measles virus (MV) hemagglutinin (H) protein is antigenically stable. The H protein is responsible for receptor binding, and is the main target of neutralizing antibodies. The immunodominant epitope, known as the hemagglutinating and noose epitope, is located near the receptor-binding site (RBS). The RBS also contains an immunodominant epitope. Loss of receptor binding correlates with an escape from the neutralization by antibodies that target the epitope at RBS. Another neutralizing epitope is located near RBS and is shielded by an N-linked sugar in certain genotype strains. However, human sera from vaccinees and measles patients neutralized all MV strains with similar efficiencies, regardless of the N-linked sugar modification or mutations at these epitopes. Two other major epitopes exist at a distance from RBS. One has an unstructured flexible domain with a linear neutralizing epitope. When MV-H forms a tetramer (dimer of dimers), these epitopes may form the dimer-dimer interface, and one of the two epitopes may also interact with the F protein. The neutralization mechanisms of antibodies that recognize these epitopes may involve inhibiting the H-F interaction or blocking the fusion cascade after MV-H binds to its receptors.