Gamma interferon-dependent, noncytolytic clearance of Sindbis virus infection from neurons in vitro
Gamma interferon-dependent, noncytolytic clearance of Sindbis virus infection from neurons in vitro
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DOI：
10.1128/jvi.79.9.5374-5385.2005
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发表时间：
2005-05-01
影响因子：
5.4
通讯作者：
Griffin, DE
中科院分区：
文献类型：
--
作者：
Burdeinick-Kerr, R;Griffin, DE
由于神经元的不可再生性，从病毒感染的中枢神经系统中恢复需要非细胞病变机制来控制病毒复制。通过抗体和干扰素(干扰素)的作用，甲型病毒性脑炎可以在没有明显神经损伤的情况下恢复。为了建立体外细胞培养体系，研究干扰素-γ介导的控制SINV在神经元中复制的机制，我们研究了两种在体外可分化的神经元细胞系：大鼠黑质细胞系CSM14.1和小鼠运动神经元细胞系NSC34对SINV感染的敏感性和干扰素-γ的反应性。未分化的CSM14.1和NSC34细胞对SINV是允许的，对病毒诱导的细胞死亡敏感。随着分化，CSM14.1细胞减少了病毒复制，并逐渐对病毒诱导的细胞死亡产生抵抗力，导致病毒复制时间延长。NSC34细胞没有完全分化，对SINV感染只产生部分抗性。CSM14.1和NSC34细胞均可通过减少SINV复制来应对干扰素-γ的预处理。分化后的CSM14.1细胞在感染干扰素-γ24 h后，细胞活力和对感染病毒的清除能力增强。在治疗后24 h内，干扰素-γ可改变病毒基因组/亚基因组RNA合成的比例，促进细胞蛋白质合成的恢复，减少病毒蛋白质合成，抑制病毒RNA转录。结论：CSM14.1细胞为研究干扰素-γ介导的成熟神经元对SINV的非细胞毒性清除提供了一个很好的模型。
Due to the nonrenewable nature of neurons, recovery from viral infection of the central nervous system requires noncytopathic mechanisms for control of virus replication. Recovery from alphavirus encephalitis can occur without apparent neurological damage through the effects of antibody and gamma interferon (IFN-gamma). To establish an in vitro cell culture system that will allow the study of mechanisms of IFN-gamma-mediated control of Sindbis virus (SINV) replication in neurons, we have characterized the susceptibility to SINV infection and IFN-gamma responsiveness of two neuronal cell lines that can be differentiated in vitro: CSM14.1, a rat nigral cell line, and NSC34, a mouse motor neuron cell line. Undifferentiated CSM14.1 and NSC34 cells were permissive for SINV and susceptible to virus-induced cell death. With differentiation, CSM14.1 cells reduced virus replication and became progressively resistant to virus-induced cell death, resulting in prolonged virus replication. NSC34 cells did not differentiate completely and became only partially resistant to SINV infection. Both CSM14.1 and NSC34 cells responded to pretreatment with IFN-gamma by decreasing SINV replication. Differentiated CSM14.1 cells treated 24 h after infection with IFN-gamma responded with increased cell viability and clearance of infectious virus. IFN-gamma treatment sequentially altered the ratio of genomic to subgenomic viral RNA synthesis, promoted recovery of cellular protein synthesis, reduced viral protein synthesis, and inhibited viral RNA transcription within 24 h after treatment. We conclude that CSM14.1 cells provide an excellent model for the study of IFN-gamma-mediated noncytolytic clearance of SINV from mature neurons.