CHARACTERIZATION OF AN ANTIGENIC DETERMINANT OF THE GLYCOPROTEIN THAT CORRELATES WITH PATHOGENICITY OF RABIES VIRUS
CHARACTERIZATION OF AN ANTIGENIC DETERMINANT OF THE GLYCOPROTEIN THAT CORRELATES WITH PATHOGENICITY OF RABIES VIRUS
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DOI：
10.1073/pnas.80.1.70
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
KOPROWSKI, H
中科院分区：
文献类型：
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作者：
DIETZSCHOLD, B;WUNNER, WH;KOPROWSKI, H
固定狂犬病病毒株对成年小鼠的致病性取决于病毒糖蛋白上抗原决定因子的存在。两种病毒中和单克隆抗体用于鉴定该决定因子。所有固定狂犬病病毒的致病性毒株都与这些抗体结合并被它们中和；非致病性菌株不能与这些单克隆抗体反应，也不能被它们中和。在1个单克隆抗体194-2存在的情况下，通过培养病毒筛选出糖蛋白改变的狂犬病毒抗原变异体。所有失去与该抗体和另一种抗体248-8反应能力的变异，对成年小鼠无致病性。对致病性亲本病毒和非致病性变异体的糖蛋白的色氨酸肽和特异性变异体色氨酸肽的氨基酸序列分析表明，致病性的变化与糖蛋白分子333位的氨基酸取代有关。非致病性变异糖蛋白基因的核苷酸序列包含一个碱基变化，证实了色氨酸肽取代亲本糖蛋白中的精氨酸-333的单氨基酸取代。显然，精氨酸-333对于抗原决定因子的完整性和狂犬病病毒在成年小鼠中产生致死感染的能力至关重要。
The pathogenicity of fixed rabies virus strains for adult mice depends on the presence of an antigenic determinant on the viral glycoprotein. Two virus-neutralizing monoclonal antibodies were used to identify this determinant. All pathogenic strains of fixed rabies virus bind to these antibodies and are neutralized by them; nonpathogenic strains fail to react with these monoclonal antibodies and are not neutralized by them. Antigenic variants of the rabies virus with altered glycoprotein were selected by growing virus in the presence of 1 monoclonal antibody, 194-2. All variants that lost their ability to react with this antibody and an additional antibody, 248-8, were found to be nonpathogenic for adult mice. Analysis of tryptic peptides of the glycoproteins of pathogenic parent virus and nonpathogenic variants and the amino acid sequence of a specific variant tryptic peptide revealed that the change in pathogenicity corresponded to an amino acid substitution at position 333 of the glycoprotein molecule. The nucleotide sequence of the nonpathogenic variant glycoprotein gene contained a base change that confirmed the single amino acid substitution in the tryptic peptide replacing arginine-333 in the parental glycoprotein. Evidently, arginine-333 is essential for the integrity of an antigenic determinant and for the ability of rabies viruses to produce lethal infection in adult mice.