Rivarola María E, de Olmos Soledad, Albrieu-Llinás Guillermo, Tauro Laura B, Gorosito-Serrán Melisa, Konigheim Brenda S, Contigiani Marta S, Gruppi Adriana
Laboratorio de Arbovirus, Instituto de Virología "Dr. J. M. Vanella", Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Laboratorio de Neuroanatomía e Histología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra - INIMEC-CONICET-UNC, Córdoba, Argentina.
Front Microbiol. 2018 Jun 7;9:1181. doi: 10.3389/fmicb.2018.01181. eCollection 2018.
Saint Louis encephalitis virus (SLEV) is a neglected flavivirus that causes severe neurological disorders. The epidemic strain of SLEV, CbaAr-4005, isolated during an outbreak in Córdoba city (Argentina), causes meningitis and encephalitis associated with neurological symptoms in a murine experimental model. Here, we identified the affected brain areas and the damage triggered by this neurotropic arbovirus. We performed a detailed analysis of brain neurodegeneration associated with CbaAr-4005 SLEV infection in mice. The motor cortex, corpus striatum and cerebellum were the most affected structures. Neurodegeneration was also found in the olfactory bulb, thalamus, hypothalamus, hippocampus, and hindbrain. SLEV infection triggered brain cell apoptosis as well as somatodendritic and terminal degeneration. In addition, we observed massive excitotoxic-like degeneration in many cortical structures. Apoptosis was also detected in the neuroblastoma cell line N2a cultured with SLEV. The results evidenced that SLEV CbaAr-4005 infection induced severe degenerative alterations within the central nervous system of infected mice, providing new information about the targets of this flavivirus infection.
圣路易斯脑炎病毒(SLEV)是一种被忽视的黄病毒,可导致严重的神经紊乱。在科尔多瓦市(阿根廷)的一次疫情暴发期间分离出的SLEV流行株CbaAr - 4005,在小鼠实验模型中会引发与神经症状相关的脑膜炎和脑炎。在此,我们确定了受这种嗜神经性虫媒病毒影响的脑区以及所引发的损伤。我们对小鼠中与CbaAr - 4005 SLEV感染相关的脑神经元变性进行了详细分析。运动皮层、纹状体和小脑是受影响最严重的结构。在嗅球、丘脑、下丘脑、海马体和后脑也发现了神经元变性。SLEV感染引发了脑细胞凋亡以及体细胞树突和终末变性。此外,我们在许多皮质结构中观察到大量类似兴奋性毒性的变性。在用SLEV培养的神经母细胞瘤细胞系N2a中也检测到了凋亡。结果表明,SLEV CbaAr - 4005感染在受感染小鼠的中枢神经系统内诱导了严重的退行性改变,为这种黄病毒感染的靶点提供了新信息。