REDUCED MOUSE NEUROVIRULENCE OF POLIOVIRUS TYPE-2 LANSING ANTIGENIC VARIANTS SELECTED WITH MONOCLONAL-ANTIBODIES
REDUCED MOUSE NEUROVIRULENCE OF POLIOVIRUS TYPE-2 LANSING ANTIGENIC VARIANTS SELECTED WITH MONOCLONAL-ANTIBODIES
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DOI：
10.1016/0042-6822(87)90136-x
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发表时间：
1987-12-01
期刊：
影响因子：
3.7
通讯作者：
RACANIELLO, VR
中科院分区：
文献类型：
--
作者：
LAMONICA, N;KUPSKY, WJ;RACANIELLO, VR
脊髓灰质炎病毒2型的兰辛株是一种小鼠适应病毒，在脑内接种后会在小鼠身上引发一种致命的瘫痪疾病。我们先前的结果表明，小鼠适应的表型映射到兰辛病毒衣壳。为了进一步确定衣壳蛋白与小鼠感染相关的区域，我们选择了一些抗原性突变体，并对它们的小鼠神经毒力进行了研究。所用的单抗针对位于病毒粒子表面的衣壳多肽VP1的免疫优势环抗原位点1。与亲本病毒相比，所选择的22个变种中有10个在小鼠脑内具有较低的神经毒力。在10个神经毒力降低的抗原变异体中，有4个变异体对温度敏感(Ts)，可在HeLa细胞中复制，其余6个变异体在HeLa细胞和母体病毒中复制。被研究的两个ts+变种在小鼠大脑中的复制能力降低。与亲本病毒相比，一个变异株在组织病理学和中枢神经系统受累模式上没有不同。在三个变异体中，神经毒力的降低与位于抗原点1内的VP1第100和101位的特定氨基酸替换有关。三个变异体的IS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瘫痪小鼠的脑中恢复的病毒被鉴定为致病病毒。在大多数情况下，脑分离株在神经毒力和抗原部位的氨基酸序列上与接种的病毒相似。从接种IS变种的瘫痪小鼠的大脑中恢复的病毒要么是TS+，要么是冷敏感的，并且已经变得更具神经毒力。这些结果表明，病毒粒子表面抗原部位的特定氨基酸变化可能导致小鼠神经毒力的降低，而不会影响培养细胞中的病毒复制。
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 is 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 is 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