Neuroscience Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Viruses. 2019 Jun 14;11(6):552. doi: 10.3390/v11060552.
When infection with lymphocytic choriomeningitis (LCMV) occurs during pregnancy, the virus can infect the fetus and injure the fetal brain. However, type, location, and severity of neuropathology differ among cases. One possible explanation for this diversity is that fetuses are infected with different viral strains. Using a rat model of congenital LCMV infection, we investigated how differences in LCMV strain (E350, WE2.2, and Clone 13) affect outcome. Rat pups received intracranial inoculations on postnatal day 4. E350 initially targeted glial cells, while WE2.2 and Clone 13 targeted neurons. The E350 strain induced focal destructive lesions, while the other strains induced global microencephaly. E350 attracted large numbers of CD8+ lymphocytes early in the disease course, while Clone 13 attracted CD4+ lymphocytes, and the infiltration occurred late. The E350 and WE2.2 strains induced large increases in expression of pro-inflammatory cytokines, while Clone 13 did not. The animals infected with E350 and WE2.2 became ataxic and performed poorly on the negative geotaxis assay, while the Clone 13 animals had profound growth failure. Thus, in the developing brain, different LCMV strains have different patterns of infection, neuropathology, immune responses and disease symptoms. In humans, different outcomes from congenital LCMV may reflect infection with different strains.
当妊娠期间发生淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染时，病毒可感染胎儿并损伤胎儿大脑。然而，病例之间的神经病理学类型、位置和严重程度存在差异。造成这种多样性的一个可能解释是，胎儿感染了不同的病毒株。我们使用大鼠先天性 LCMV 感染模型，研究了 LCMV 株（E350、WE2.2 和 Clone 13）的差异如何影响结局。大鼠幼仔在产后第 4 天接受颅内接种。E350 株最初靶向神经胶质细胞，而 WE2.2 和 Clone 13 株靶向神经元。E350 株诱导局灶性破坏性病变，而其他株诱导全脑小畸形。E350 在疾病早期吸引大量 CD8+淋巴细胞，而 Clone 13 株吸引 CD4+淋巴细胞，且浸润发生较晚。E350 和 WE2.2 株诱导促炎细胞因子的大量表达增加，而 Clone 13 株则没有。感染 E350 和 WE2.2 的动物出现共济失调，在负趋地性试验中表现不佳，而 Clone 13 动物生长严重不良。因此，在发育中的大脑中，不同的 LCMV 株具有不同的感染、神经病理学、免疫反应和疾病症状模式。在人类中，先天性 LCMV 的不同结局可能反映了感染不同的株。
