Alteration of amino acid 101 within capsid protein VP-1 changes the pathogenicity of Theiler's murine encephalomyelitis virus.
Alteration of amino acid 101 within capsid protein VP-1 changes the pathogenicity of Theiler's murine encephalomyelitis virus.
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在衣壳蛋白VP-1中的氨基酸101改变改变了Theiler鼠脑脊髓炎病毒的致病性。
DOI：
10.1084/jem.170.6.2037
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发表时间：
1989-12-01
影响因子：
15.3
通讯作者：
FUJINAMI, RS
中科院分区：
文献类型：
--
作者：
ZURBRIGGEN, A;HOGLE, JM;FUJINAMI, RS
慢性泰勒氏鼠脑脊髓炎病毒感染易感小鼠是人类脱髓鞘疾病的动物模型。之前我们描述了感染变异病毒的免疫活性 SJL/J 小鼠中枢神经系统疾病的改变和减少模式。使用识别泰勒病毒衣壳蛋白 VP-1 的中和单克隆抗体选择该变异病毒 H7A6-2。在这里，我们通过 ELISA 和中和测定以及对病毒 RNA 基因组的选定区域进行测序来表征变异病毒，并将变化与疾病联系起来。该变异病毒在 VP-1 的中和表位内含有一个单点突变。这种核苷酸变化导致 VP-1 氨基酸 101 处的氨基酸替换，即苏氨酸（野生型）变为异亮氨酸（变体）。基于序列比对和相关门戈病毒已知结构的模型构建表明，改变的氨基酸位于病毒表面暴露的环中，位于被认为是受体结合位点的位点的外围。 ELISA、中和测定和直接 RNA 测序的结果首次提供了精确绘制神经毒力的重要结构决定因素的机会。
Chronic Theiler's murine encephalomyelitis virus infection of susceptible mice is an animal model for human demyelinating diseases. Previously we described an altered and diminished pattern of central nervous system disease in immunocompetent SJL/J mice infected with a variant virus. This variant virus H7A6-2 was selected with a neutralizing mAb recognizing the capsid protein VP-1 of Theiler's virus. Here we characterize the variant virus by ELISA and neutralization assays and by sequencing selected regions of the viral RNA genome and relate the alteration to disease. The variant virus contains one single point mutation within a neutralizing epitope of VP- 1. This nucleotide change lead to an amino acid replacement at amino acid 101 of VP-1, a threonine (wild type) to an isoleucine (variant). Model building based on sequence alignments and the known structure of the related Mengo virus indicates that the altered amino acid is located in an exposed loop on the surface of the virus at the periphery of a site that has been proposed to be the receptor binding site. The results of ELISA, neutralization assay, and direct RNA sequencing provide for the first time an opportunity to precisely map an important structural determinant of neurovirulence.
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