Boulaire Jérôme, Zhao Ying, Wang Shu
Institute of Bioengineering and Nanotechnology, Singapore.
J Neurochem. 2009 Jun;109(5):1203-14. doi: 10.1111/j.1471-4159.2009.06015.x. Epub 2009 Apr 17.
Recombinant baculoviral vectors efficiently transduce several types of cells in the brain. To characterize host responses to virus challenge, thus verifying the suitability of using baculovirus for the development of gene therapy strategies in the central nervous system, we used cDNA microarray technology to examine in vitro and in vivo global cellular gene expression profiles in the rat brain, cultured human astrocytes and human neuronal cells after viral transduction. We demonstrated that the transduction induced host antiviral responses as a major reaction in all three types of samples profiled. The related genes were mainly those associated with innate immunity, including several of the genes involved in Toll-like receptor signaling pathway and cytokine-cytokine receptor interaction. These findings should be useful in understanding the molecular basis for neural cell response to baculoviral transduction and in guiding rational therapeutic applications of baculoviral vectors in the central nervous systems.
重组杆状病毒载体可有效地转导脑内多种类型的细胞。为了表征宿主对病毒攻击的反应，从而验证使用杆状病毒开发中枢神经系统基因治疗策略的适用性，我们使用cDNA微阵列技术检测了病毒转导后大鼠脑、培养的人星形胶质细胞和人神经元细胞的体外和体内整体细胞基因表达谱。我们证明，转导在所有三种分析的样本类型中均诱导宿主抗病毒反应作为主要反应。相关基因主要是那些与先天免疫相关的基因，包括参与Toll样受体信号通路和细胞因子-细胞因子受体相互作用的几个基因。这些发现将有助于理解神经细胞对杆状病毒转导反应的分子基础，并指导杆状病毒载体在中枢神经系统中的合理治疗应用。
