Identification of two amino acids in the hemagglutinin glycoprotein of measles virus (MV) that govern hemadsorption, HeLa cell fusion, and CD46 downregulation: Phenotypic markers that differentiate vaccine and wild-type MV strains
Identification of two amino acids in the hemagglutinin glycoprotein of measles virus (MV) that govern hemadsorption, HeLa cell fusion, and CD46 downregulation: Phenotypic markers that differentiate vaccine and wild-type MV strains
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DOI：
10.1128/jvi.70.7.4200-4204.1996
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发表时间：
1996-07-01
影响因子：
5.4
通讯作者：
Buckland, R
中科院分区：
文献类型：
--
作者：
Lecouturier, V;Fayolle, J;Buckland, R
我们已经使用麻疹病毒（MV）的血凝素（H）糖蛋白的定点突变，以研究MV疫苗株和最近分离的野生型MV株之间观察到的表型差异的分子基础。前者下调CD 46，推定的细胞受体MV，是阳性的血细胞吸附，并在HeLa细胞中的融合，而后者是阴性的这些表型标记。特别是CD 46下调可能对MV感染的免疫病理学产生深远的影响，因为该分子保护细胞免受补体裂解。将来自疫苗样Halle MV毒株的H蛋白中的位置451和481处的两个氨基酸缬氨酸和酪氨酸分别突变成来自野生型Ma 93 F MV毒株的H蛋白中的对应物谷氨酸和天冬酰胺（产生V451 E/Y 481 N双突变）消除了CD 46下调、HeLa细胞融合和血细胞吸附，通过匡威双突变，使Ma 93 F H蛋白（E451 V/N481 Y）具有CD 16下调、融合和血细胞吸附等功能。这些结果的AIV疫苗的设计和MV感染中的CD 46的作用的后果进行了讨论。
We have used site-directed mutagenesis of the hemagglutinin (H) glycoprotein of measles virus (MV) to investigate the molecular basis for the phenotypic differences observed between MV vaccine strains and recently isolated wild-type MV strains. The former downregulate CD46, the putative cellular receptor of MV, are positive for hemadsorption, and are fusogenic in HeLa cells, whereas the latter are negative for these phenotypic markers. CD46 downregulation in particular, could have profound consequences for the immunopathology of MV infection, as this molecule protects the cell from complement lysis. Mutagenesis of two amino acids, valine and tyrosine at positions 451 and 481, respectively, in the H protein from the vaccine-like Halle MV strain to their counterparts, glutamate and asparagine, in the H protein from the wild-type Ma93F MV strain (creating the V451E/Y481N double mutation) abrogated CD46 downregulation, HeLa cell fusion, and hemadsorption, The converse double mutagenesis of the Ma93F H protein (E451V/N481Y) transferred the CD16-downregulating, fusogenic, and hemadsorption functions to this protein, The data provide the first mapping study of the functional domains of MV H. The consequences of these results for AIV vaccine design and the role of CD46 in MV infection are discussed.