Abstract：
Lentiviruses are suitable to transfer potential therapeutic genes into non-replicating cells such as neurons, but systematic in vivo studies on transduction of neural cells within the complete brain are missing. We analysed the distribution of transduced cells with respect to brain structure, virus tropism, numbers of transduced neurons per brain, and influence of the Vpx or Vpr accessory proteins after injection of vectors based on SIVsmmPBj, HIV-2, and HIV-1 lentiviruses into the right striatum of the mouse brain. Transduced cells were found ipsilaterally around the injection canal, in corpus striatum and along corpus callosum, irrespective of the vector type. All vectors except HIV-2SEW transduced also single cells in the olfactory bulb, hippocampus, and cerebellum. Vector HIV-2SEW was the most neuron specific. However, vectors PBjSEW and HIV-1SEW transduced more neurons per brain (means 41,299 and 32,309) than HIV-2SEW (16,102). In the presence of Vpx/Vpr proteins, HIV-2SEW(Vpx) and HIV-1SEW(Vpr) showed higher overall transduction efficiencies (30,696 and 27,947 neurons per brain) than PBjSEW(Vpx) (6636). The distances of transduced cells from the injection canal did not differ among the viruses but correlated positively with the numbers of transduced neurons. The presence of Vpx/Vpr did not increase the numbers of transduced neurons. Parental virus type and the vector equipment seem to influence cellular tropism and transduction efficiency. Thus, precision of injection and choice of virus pseudotype are not sufficient when targeted lentiviral vector transduction of a defined brain cell population is required.
摘要：
慢病毒适用于将潜在的治疗基因转移到非复制细胞如神经元，但是缺乏关于整个大脑中神经细胞转导的系统体内研究。我们分析了转导细胞相对于大脑结构的分布，病毒嗜性，每个大脑的转导神经元数量，以及注射基于SIVsmmPBj的载体后Vpx或Vpr辅助蛋白的影响，HIV-2和HIV-1慢病毒进入小鼠大脑的右侧纹状体。在注射管周围同侧发现了转导的细胞，在纹状体和call体，与向量类型无关。除HIV-2SEW外，所有载体也转导嗅球中的单细胞，海马体,还有小脑.载体HIV-2SEW是最具神经元特异性的。然而,载体PBjSEW和HIV-1SEW比HIV-2SEW（16,102）每个脑转导更多的神经元（平均41,299和32,309）。在存在Vpx/Vpr蛋白的情况下，HIV-2SEW(Vpx)和HIV-1SEW(Vpr)显示出比PBjSEW(Vpx)(6636)更高的总转导效率(每个脑30,696和27,947个神经元)。转导细胞与注射管的距离在病毒之间没有差异，但与转导神经元的数量呈正相关。Vpx/Vpr的存在没有增加转导的神经元的数量。亲本病毒类型和载体设备似乎会影响细胞嗜性和转导效率。因此，当需要确定的脑细胞群的靶向慢病毒载体转导时,注射的精确性和病毒假型的选择是不够的.
