CELL-FUSION BY THE ENVELOPE GLYCOPROTEINS OF PERSISTENT MEASLES VIRUSES WHICH CAUSED LETHAL HUMAN BRAIN DISEASE
CELL-FUSION BY THE ENVELOPE GLYCOPROTEINS OF PERSISTENT MEASLES VIRUSES WHICH CAUSED LETHAL HUMAN BRAIN DISEASE
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DOI：
10.1128/jvi.67.3.1493-1502.1993
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发表时间：
1993-03-01
影响因子：
5.4
通讯作者：
ROSE, JK
中科院分区：
文献类型：
--
作者：
CATTANEO, R;ROSE, JK
麻疹病毒（MV）很少引起人类中枢神经系统的致命性疾病，其特征在于病毒包膜蛋白表达减少和缺乏病毒出芽。MV包膜含有两种完整的膜蛋白，称为融合（F）蛋白和血凝素（H）蛋白，以及膜相关基质（M）蛋白。先前对来自尸检材料的MV基因的分析表明，M蛋白和F蛋白的细胞内结构域经常因突变而急剧改变。在这里，我们提出的证据表明，截短的F蛋白胞内结构域不损害融合功能，我们认为，这种改变干扰病毒出芽。出乎意料的是，功能性F和H蛋白的某些组合不能诱导合胞体形成，这一观察结果表明细胞融合需要特异性F-H蛋白相互作用。我们还发现，持久性MV的四个H蛋白中有三个在细胞内转运、寡糖修饰、二聚化和融合辅助功能方面有缺陷。因此，在感染的终末阶段在脑中复制的MV通常在M蛋白和两个完整的膜蛋白中有缺陷。虽然M蛋白似乎完全不起作用，但似乎需要部分保留F蛋白功能和H蛋白功能，可能是为了允许局部细胞融合。F和H蛋白的某些细微变化可能有助于疾病的发展。
Measles virus (MV) rarely induces lethal diseases of the human central nervous system characterized by reduced expression of the viral envelope proteins and by lack of viral budding. The MV envelope contains two integral membrane proteins, termed fusion (F) protein and hemagglutinin (H) protein, and a membrane-associated matrix (M) protein. Previously analysis of MV genes from autopsy material indicated that the M protein and the F protein intracellular domain are often drastically altered by mutations. Here, we present evidence that truncation of the F protein intracellular domain does not impair fusion function, and we suggest that this alteration interferes with viral budding. Unexpectedly, certain combinations of functional F and H proteins were unable to induce syncytium formation, an observation suggesting that specific F-H protein interactions are required for cell fusion. We also found that three of four H proteins of persistent MVs are defective in intracellular transport, oligosaccharide modification, dimerization, and fusion helper function. Thus, MVs replicating in the brain at the terminal stage of infection are typically defective in M protein and in the two integral membrane proteins. Whereas the M protein appears dispensable altogether, partial preservation of F-protein function and H-protein function seems to be required, presumably to allow local cell fusion. Certain subtle alterations of the F and H proteins may be instrumental for disease development.