A cell fusion-inhibiting monoclonal antibody binds to the presumed stalk domain of the human parainfluenza type 2 virus hemagglutinin-neuraminidase protein.

A cell fusion-inhibiting monoclonal antibody binds to the presumed stalk domain of the human parainfluenza type 2 virus hemagglutinin-neuraminidase protein.
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细胞融合抑制单克隆抗体与人副流感 2 型病毒血凝素神经氨酸酶蛋白的假定茎结构域结合。

DOI:
10.1006/viro.1995.1035
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发表时间:
1995
期刊:
影响因子:
3.7
通讯作者:
M. Tsurudome
M. Tsurudome
中科院分区:
医学3区
文献类型:
--
作者:
T. Yuasa;M. Kawano;N. Tabata;M. Nishio;S. Kusagawa;H. Komada;H. Matsumura;Y. Ito;M. Tsurudome

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被引文献

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先前,我们获得了针对人副流感病毒2型(PIV 2)的血凝素-神经氨酸酶(HN)蛋白的中和性单克隆抗体,该抗体能够防止细胞融合而不影响血凝和神经氨酸酶活性。在本研究中,在单克隆抗体的压力下,获得了四个PIV 2的逃逸突变体。有趣的是,每个突变体的HN蛋白被证明有两个氨基酸取代,其中一个是在83 Asn或91 Lys,另一个是在150 Leu,160 Ala或186 Met。其中一个突变体命名为F13,其HN蛋白的83 Asn和186 Met发生了替换,尽管它在HeLa细胞中多次复制,但它不能引起细胞融合,而其他突变体形成典型的合胞体细胞。F13融合蛋白(F)的氨基酸序列与野生型F蛋白一致,蛋白表达分析表明,F13的低融合表型是由于其突变的HN蛋白,其对单克隆抗体的抗原性被83 Asn的单突变所消除。这些观察结果表明,该单克隆抗体的主要表位位于HN蛋白的假定茎域,这可能在促进细胞融合中起重要作用。
Previously, we obtained a neutralizing monoclonal antibody directed against the hemagglutinin-neuraminidase (HN) protein of human parainfluenza type 2 virus (PIV2), which was able to prevent cell fusion without affecting the hemagglutinating and neuraminidase activities. In this study, four escape mutants of PIV2 have been obtained under pressure of the monoclonal antibody. Intriguingly, the HN protein of each mutant proved to have two amino acid substitutions, one of which is at 83Asn or 91Lys, and another one is at 150Leu, 160Ala, or 186Met. One mutant designated F13, which has substitutions at 83Asn and 186Met in the HN protein, could not cause cell fusion in HeLa cells despite its multiple replication, while the other mutants formed typical syncytial cells. The deduced amino acid sequence of F13 fusion (F) protein proved to be identical to that of wild-type F protein, and furthermore, protein expression analyses have revealed that the low-fusion phenotype of F13 was due to its mutated HN protein, whose antigenicity to the monoclonal antibody was abolished by the single mutation at 83Asn. These observations have suggested that the principal epitope for the monoclonal antibody resides in the presumed stalk domain of the HN protein, which may play an important role in promoting cell fusion.