Sindbis virus-induced neuronal death is both necrotic and apoptotic and is ameliorated by N-methyl-D-aspartate receptor antagonists
Sindbis virus-induced neuronal death is both necrotic and apoptotic and is ameliorated by N-methyl-D-aspartate receptor antagonists
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DOI：
10.1128/jvi.75.15.7114-7121.2001
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发表时间：
2001-08-01
影响因子：
5.4
通讯作者：
Griffin, DE
中科院分区：
文献类型：
--
作者：
Nargi-Aizenman, JL;Griffin, DE
病毒感染神经元可导致不同的结果，从潜伏性和非细胞溶解性感染到细胞死亡。病毒通过诱导细胞凋亡或坏死直接杀死神经元，或间接作为宿主免疫反应的结果。Sindbis病毒（SV）是一种在体外和体内诱导凋亡细胞死亡的甲病毒。然而，在甲病毒感染诱导的神经元死亡中，凋亡变化并不总是明显的。延时成像显示，sv感染的原代皮层神经元表现出凋亡和坏死的形态学特征，培养物中未感染的神经元也死亡。谷氨酸受体n -甲基- d -天冬氨酸（NMDA）亚型拮抗剂保护神经元免受sv诱导的死亡，而不影响病毒复制或sv诱导的凋亡细胞死亡。这些结果提供了证据，证明SV感染激活神经毒性通路，导致异常的NMDA受体刺激和对感染和未感染神经元的损伤。
Virus infection of neurons leads to different outcomes ranging from latent and noncytolytic infection to cell death. Viruses kill neurons directly by inducing either apoptosis or necrosis or indirectly as a result of the host immune response. Sindbis virus (SV) is an alphavirus that induces apoptotic cell death both in vitro and in vivo. However, apoptotic changes are not always evident in neurons induced to die by alphavirus infection. Time lapse imaging revealed that SV-infected primary cortical neurons exhibited both apoptotic and necrotic morphological features and that uninfected neurons in the cultures also died. Antagonists of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors protected neurons from SV-induced death without affecting virus replication or SV-induced apoptotic cell death. These results provide evidence that SV infection activates neurotoxic pathways that result in aberrant NMDA receptor stimulation and damage to infected and uninfected neurons.