Fleming J O, Trousdale M D, Bradbury J, Stohlman S A, Weiner L P
Department of Neurology, School of Medicine, University of Southern California, Los Angeles 90033.
Microb Pathog. 1987 Jul;3(1):9-20. doi: 10.1016/0882-4010(87)90033-7.
The molecular basis for demyelination induced by the neurotropic murine coronavirus JHM (JHMV or MHV4) is unknown. We have attempted to explore this issue by using neutralizing monoclonal antibodies specific for the major JHMV glycoprotein (E2) to select sets of neutralization resistant (NR) antigenic variant viruses. Monoclonal antibodies J.7.2 and J.2.2 bind to topographically distinct sites on E2. NR variants selected with J.7.2, like parental JHMV, predominantly cause a fatal encephalitis when given intracerebrally to mice, while J.2.2-selected NR variants cause a subacute disease characterized by paralysis and severe demyelination. We report here that consecutive selection with both J.2.2 and J.7.2 monoclonal antibodies results in NR variants which are markedly attenuated in both encephalitic potential and ability to induce demyelination. Analysis of the different variants suggests that the subregion of E2 bound by monoclonal antibody J.7.2 may be a critical viral determinant of paralysis and demyelination in this model system.
嗜神经性鼠冠状病毒JHM（JHMV或MHV4）诱导脱髓鞘的分子基础尚不清楚。我们试图通过使用针对主要JHMV糖蛋白（E2）的中和单克隆抗体来选择一组抗中和（NR）抗原变异病毒，以探讨这个问题。单克隆抗体J.7.2和J.2.2与E2上拓扑结构不同的位点结合。用J.7.2选择的NR变异株，与亲代JHMV一样，脑内接种小鼠时主要引起致命性脑炎，而用J.2.2选择的NR变异株引起以麻痹和严重脱髓鞘为特征的亚急性疾病。我们在此报告，用J.2.2和J.7.2单克隆抗体连续选择会产生NR变异株，其脑炎潜力和诱导脱髓鞘的能力均显著减弱。对不同变异株的分析表明，单克隆抗体J.7.2所结合的E2亚区域可能是该模型系统中麻痹和脱髓鞘的关键病毒决定因素。
