A neutralization-resistant Theiler's virus variant produces an altered disease pattern in the mouse central nervous system.
A neutralization-resistant Theiler's virus variant produces an altered disease pattern in the mouse central nervous system.
复制标题
一种具有中和抗性的泰勒病毒变种会在小鼠中枢神经系统中产生改变的疾病模式。
DOI：
10.1128/jvi.63.4.1505-1513.1989
复制
发表时间：
1989
影响因子：
5.4
通讯作者：
Fujinami,RS
中科院分区：
文献类型：
--
作者：
Zurbriggen,A;Fujinami,RS
鼠脑脊髓炎病毒感染小鼠是人类脱髓鞘疾病的动物模型。为了进一步确定该病毒在疾病过程中的作用，我们选择了一种抗VP-1单克隆抗体中和的病毒变体。然后将该病毒变体注射到SJL/J小鼠体内。比较了变异病毒和野生型病毒感染小鼠的中枢神经系统组织。在脑内，两组在注射部位周围炎症浸润的分布和病毒抗原阳性细胞的数量在观察期的第一周内没有观察到大的差异。相反，在脊髓中，变异病毒感染小鼠和野生型病毒感染小鼠在炎性病变的数量、感染细胞的数量以及与时间有关的区域的大小方面存在主要差异。免疫组化法发现，感染后1周脊髓内感染细胞数量相等，但在此之后，野生型病毒感染小鼠的感染细胞数量继续增加，而变异病毒感染小鼠的病毒阳性细胞数量逐渐减少。因此，在变异病毒感染的动物中，含病毒抗原细胞的数量在1周后达到峰值。相反，接种野生型病毒的小鼠脊髓中感染细胞的数量稳步增加，直到第8周。此时（第8周），脊髓内未观察到更多的变异病毒抗原阳性细胞。免疫组化观察的两组间中枢神经系统组织斑块分析证实了这些差异。在脑内和脊髓内分别隔离2周和4周后均未分离到传染性变异病毒，而在观察期（隔离12周）结束前仍可检测到传染性野生型病毒。从变异病毒感染小鼠中分离出的病毒仍保持中和抗性表型。这些研究强调了泰勒氏病毒VP-1在决定神经毒力方面的重要生物体内活性。
Theiler's murine encephalomyelitis virus infection of mice is an animal model for human demyelinating diseases. To further define the role of this virus in the disease process, we selected a virus variant resistant to neutralization by a monoclonal antibody to VP-1. This virus variant was then injected into SJL/J mice. Central nervous system tissue was compared between variant virus- and wild-type virus-infected mice. Within the brain, no large differences were observed between the two groups as to the distribution of inflammatory infiltrates around the injection site and the number of viral antigen-positive cells during the first weeks of the observation period. In contrast, in the spinal cord major differences were found between variant virus- and wild-type virus-infected mice regarding the number of inflammatory lesions, infected cells, and the size of the areas involved with time. By immunohistochemistry, equivalent numbers of infected cells could be found in the spinal cord 1 week postinfection (p.i.): however, after that time, the number of infected cells in the wild-type virus-infected mice continued to increase, whereas the virus-positive cells from the variant virus-infected mice gradually decreased. Thus, the number of viral antigen-containing cells peaked by 1 week p.i. in the variant virus-infected animals. Conversely, the number of infected cells in the spinal cords from mice inoculated with wild-type virus steadily increased until 8 weeks p.i. At this time (8 weeks p.i.), no more variant virus antigen-positive cells could be observed within the spinal cord. Plaque assay of central nervous system tissue confirmed these differences between the two groups observed by immunohistochemistry. No infectious variant virus could be isolated after 2 weeks p.i. from the brain and 4 weeks p.i. from the spinal cord, whereas infectious wild-type virus could be detected up to the end of the observation period (12 weeks p.i.). Virus which was isolated from variant virus-infected mice still retained the neutralization-resistant phenotype. These studies emphasize the important biological in vivo activity of Theiler's virus VP-1 in determining neurovirulence.