La Monica N, Kupsky W J, Racaniello V R
Department of Microbiology, Columbia University of Physicians & Surgeons, New York, New York 10032.
Virology. 1987 Dec;161(2):429-37. doi: 10.1016/0042-6822(87)90136-x.
The Lansing strain of poliovirus type 2 is a mouse-adapted virus that induces a fatal paralytic disease in mice after intracerebral inoculation. Our previous results indicated that the mouse-adapted phenotype maps to the Lansing viral capsid. To further define regions of the capsid that are specifically involved in the infection of mice, antigenic variants resistant to neutralization with monoclonal antibodies were selected, and their mouse neurovirulence was studied. The monoclonal antibodies used were directed against antigenic site 1, an immunodominant loop of capsid polypeptide VP1 located on the virion surface. Ten of twenty-two variants selected had lower intracerebral neurovirulence in mice when compared to the parental virus. Four of the ten antigenic variants with reduced neurovirulence were temperature sensitive (ts) for replication in HeLa cells, while the remaining six variants replicated in HeLa cells as well as the parent virus. Two ts+ variants that were studied had a reduced ability to replicate in the mouse brain. There was no difference in the histopathology and pattern of involvement in the central nervous system of one variant compared to the parent virus. In three variants, reduction of neurovirulence correlated with specific amino acid substitutions at positions 100 and 101 of VP1, located within antigenic site 1. The ts phenotype in three variants was associated with a single amino acid deletion at position 105. Virus recovered from the brain of paralyzed mice that had been inoculated with the antigenic variants was characterized to identify the virus causing disease. In most cases, brain isolates resembled the inoculated virus in neurovirulence and amino acid sequence at the antigenic site. Virus recovered from brains of paralyzed mice that had been inoculated with the ts variants was either ts+ or cold sensitive, and had become more neurovirulent. These results suggest that specific amino acid changes within an antigenic site on the virion surface may result in reduction of mouse neurovirulence without affecting viral replication in cultured cells.
脊髓灰质炎病毒2型的兰辛株是一种适应小鼠的病毒，脑内接种后可在小鼠中诱发致命的麻痹性疾病。我们之前的结果表明，适应小鼠的表型定位于兰辛病毒衣壳。为了进一步确定衣壳中与小鼠感染特别相关的区域，我们选择了对单克隆抗体中和具有抗性的抗原变异体，并研究了它们的小鼠神经毒力。所使用的单克隆抗体针对抗原位点1，这是位于病毒粒子表面的衣壳多肽VP1的一个免疫显性环。与亲本病毒相比，在所选的22个变异体中，有10个在小鼠中的脑内神经毒力较低。10个神经毒力降低的抗原变异体中有4个在HeLa细胞中复制时对温度敏感（ts），而其余6个变异体在HeLa细胞中的复制情况与亲本病毒相同。研究的两个ts+变异体在小鼠脑中的复制能力降低。与亲本病毒相比，一个变异体在中枢神经系统中的组织病理学和受累模式没有差异。在三个变异体中，神经毒力的降低与位于抗原位点1内的VP1第100和101位的特定氨基酸取代相关。三个变异体中的ts表型与第105位的单个氨基酸缺失有关。从接种了抗原变异体的麻痹小鼠脑中回收的病毒经过鉴定以确定引起疾病的病毒。在大多数情况下，脑分离株在神经毒力和抗原位点的氨基酸序列方面与接种的病毒相似。从接种了ts变异体的麻痹小鼠脑中回收的病毒要么是ts+要么对冷敏感，并且神经毒力变得更强。这些结果表明，病毒粒子表面抗原位点内的特定氨基酸变化可能导致小鼠神经毒力降低，而不影响病毒在培养细胞中的复制。
