The murine double-stranded RNA-dependent protein kinase PKR and the murine 2′,5′-oligoadenylate synthetase-dependent RNase L are required for IFN-β-mediated resistance against herpes simplex virus type 1 in primary trigeminal ganglion culture
The murine double-stranded RNA-dependent protein kinase PKR and the murine 2′,5′-oligoadenylate synthetase-dependent RNase L are required for IFN-β-mediated resistance against herpes simplex virus type 1 in primary trigeminal ganglion culture
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DOI：
10.1016/s0042-6822(03)00298-8
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发表时间：
2003-08-15
期刊：
影响因子：
3.7
通讯作者：
Carr, DJJ
中科院分区：
文献类型：
--
作者：
Al-Khatib, K;Williams, BRG;Carr, DJJ
进行研究以评价表达鼠干扰素-β（IFN-β）转基因（Ad：IFN-β）的腺病毒构建体在原代三叉神经节细胞培养物中对抗1型单纯疱疹病毒（HSV-1）感染的功效。根据感染复数（m.o.i.）的腺病毒载体（0.5-50.0）。此外，神经元是腺病毒转导的主要靶点。与用Ad：IFN-β转导的细胞或未转导的TG培养物对照相比，用Ad：IFN-β转导的TG培养物显示病毒滴度降低高达19倍。用Ad转导：IFN-β上调两个关键的抗病毒基因，双链RNA依赖性蛋白激酶R（PKR）和2 '，5'-寡腺苷酸合成酶（OAS）。PKR或RNA酶L（OAS的下游效应分子）的缺乏减弱了Ad：IFN-β对HSV-1复制的功效，暗示PKR和OAS/RNA酶系统在TG细胞中建立IFN诱导的对HSV-1的抗性中的关键作用。(C)2003 Elsevier Science（美国）。All rights reserved.
A study was undertaken to evaluate the efficacy of an adenoviral construct expressing the murine interferon-beta (IFN-beta) transgene (Ad:IFN-beta) against herpes simplex virus type 1 (HSV-1) infection in a primary trigeminal ganglion TG) cell culture. The transduction efficiency ranged from 0.2 to 11.0% depending on the multiplicity of infection (m.o.i.) of the adenoviral vector (0.5-50.0). Moreover, neurons were the main target of the adenoviral transduction. TG cultures transduced with Ad:IFN-beta displayed up to a 19-fold reduction in viral titers compared with cells transduced with an Ad:Null or nontransduced TG culture controls. Transduction with Ad:IFN-beta up-regulated two critical antiviral genes, double-stranded RNA-dependent protein kinase R (PKR) and 2',5'-oligoadenylate synthetase (OAS). The absence of PKR or RNase L (downstream effector molecule of OAS) attenuated Ad:IFN-beta efficacy against HSV-1 replication, implicating a critical role for PKR and OAS/RNase systems in the establishment of IFN-induced resistance against HSV-1 in TG cells. (C) 2003 Elsevier Science (USA). All rights reserved.