ANTIGENIC DETERMINANTS OF MEASLES-VIRUS HEMAGGLUTININ ASSOCIATED WITH NEUROVIRULENCE
ANTIGENIC DETERMINANTS OF MEASLES-VIRUS HEMAGGLUTININ ASSOCIATED WITH NEUROVIRULENCE
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DOI：
10.1128/jvi.68.3.1486-1493.1994
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发表时间：
1994-03-01
影响因子：
5.4
通讯作者：
RIMA, BK
中科院分区：
文献类型：
--
作者：
LIEBERT, UG;FLANAGAN, SG;RIMA, BK
在我们建立的麻疹脑炎大鼠模型中，研究了针对麻疹病毒CAM/R401株血凝素蛋白的6个表位群的特异性单抗的体内生物学活性。当将一些单抗注射到感染麻疹病毒的乳鼠的腹膜内时，一些单抗改变了疾病过程，并防止了在未经治疗的动物中出现的坏死性脑病。对麻疹病毒脑分离株的分析显示，出现了抵抗被动转移的选择性单抗而不与其他单抗中和的变异体。在体外也分离到了单抗逃逸突变体，其神经毒力在动物模型中有所不同。来自麻疹病毒血凝素基因的序列数据定位了位于氨基酸残基368和396之间的血凝素蛋白的一个主要抗原性表面决定簇，它可能对神经毒力具有重要的功能。这些数据表明，抗体与麻疹病毒H蛋白的相互作用在筛选神经毒力变异体中起着重要作用。这些变异株具有不同于亲本CAM病毒的生物学特性。
The biological activity of monoclonal antibodies specific for the hemagglutinin protein of measles virus strain CAM recognizing six epitope groups according to their binding properties to measles virus strain CAM/R401 was investigated in vivo in our rat model of measles encephalitis. When injected intraperitoneally into measles virus-infected suckling rats, some monoclonal antibodies modified the disease process and prevented the necrotizing encephalopathy seen in untreated animals. The analysis of measles virus brain isolates revealed emergence of variants that resisted neutralization with the passively transferred selecting monoclonal antibody but not with other monoclonal antibodies. Monoclonal antibody escape mutants were also isolated in vitro, and their neurovirulence varied in the animal model. Sequence data from the hemagglutinin gene of measles virus localize a major antigenic surface determinant of the hemagglutinin protein between amino acid residues 368 and 396, which may be functionally important for neurovirulence. The data indicate that the interaction of antibodies with the measles virus H protein plays an important role in the selection of neurovirulent variants. These variants have biological properties different from those of the parent CAM virus.