Poliovirus replication and spread in primary neuron cultures
Poliovirus replication and spread in primary neuron cultures
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DOI：
10.1016/j.virol.2005.05.032
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发表时间：
2005-09-15
期刊：
影响因子：
3.7
通讯作者：
Rall, GF
中科院分区：
文献类型：
--
作者：
Daley, JK;Gechman, LA;Rall, GF
虽然一些嗜神经病毒在进入脑实质后引起中枢神经系统（CNS）快速病变，但在外周具有细胞溶解性的其他病毒要么导致很少的神经病理，要么与持续感染的中枢神经系统疾病病程延长有关。其中一种病毒是脊髓灰质炎病毒（PV），它是一种极具裂解性的RNA病毒，需要表达脊髓灰质炎病毒受体（PVR） CD155才能感染。为了比较PV在神经元和非神经元细胞类型中的感染动力学，我们从CD155（+）转基因胚胎中分离海马原代神经元和成纤维细胞，用PV的Mahoney和Sabin菌株感染。尽管在这些体外培养物中感染水平相似，与成纤维细胞相比，pv感染的神经元在感染过程中产生的感染性颗粒少100倍，并且pv感染的神经元的死亡延迟了大约48小时。神经元中的传播主要通过突触传递发生，并且依赖于cd155。总之，这些结果表明，与非神经元细胞相比，神经元中PV复制、传播和随后细胞死亡的幅度和速度都有所降低，这意味着细胞特异性的复制效应可能会影响病毒的发病机制。(c) 2005爱思唯尔公司版权所有。
While some neurotropic viruses cause rapid central nervous system (CNS) disease upon entry into the brain parenchyma, other viruses that are cytolytic in the periphery either result in little neuropathology or are associated with a protracted course of CNS disease consistent with persistent infection. One such virus, poliovirus (PV), is an extremely lytic RNA virus that requires the expression of CD155, the poliovirus receptor (PVR), for infection. To compare the kinetics of PV infection in neuronal and non-neuronal cell types, primary hippocampal neurons and fibroblasts were isolated from CD155(+) transgenic embryos and infected with the Mahoney and Sabin strains of PV. Despite similar levels of infection in these ex vivo cultures, PV-infected neurons produced 100-fold fewer infectious particles as compared to fibroblasts throughout infection, and death of PV-infected neurons was delayed approximately 48 h. Spread in neurons occurred primarily by trans-synaptic transmission and was CD155-dependent. Together, these results demonstrate that the magnitude and speed with which PV replication, spread, and subsequent cell death occur in neurons is decreased as compared to non-neuronal cells, implicating cell-specific effects on replication that may then influence viral pathogenesis. (c) 2005 Elsevier Inc. All rights reserved.