van Marle Guido, Antony Joseph M, Silva Claudia, Sullivan Andrea, Power Christopher
Department of Microbiology and Infectious Diseases, University of Calgary, Calgary AB, Canada.
AIDS. 2005 Nov 4;19(16):1781-91. doi: 10.1097/01.aids.0000189854.06194.87.
To study the effects of HIV-1 and feline immunodeficiency virus (FIV) on neural stem cell viability, together with the neurotrophic properties of growth hormone (GH) in models of pediatric neuroAIDS.
Mouse neural stem cells were infected in vitro with a Sindbis virus vector (SIN-HIVenv) expressing the envelope protein from the brain-derived HIV-1 strain JR-FL using a vector expressing enhanced green fluorescent protein (SIN-EGFP) as control. Cell survival and alterations in expression of neural stem cell markers upon GH treatment was assessed. Neonatal cats were infected with a neurovirulent FIV strain and 6 weeks after infection treated with GH for 6 weeks. Twelve weeks post-infection, neural progenitor cell marker expression, neuronal loss and neuroinflammation in brain were examined using real time reverse transcription-PCR and immunohistochemical analyses.
HIV-1 envelope expression in neural stem cells reduced nestin expression (P < 0.05) and induced cell death (P < 0.001), which was blocked by GH. In the frontal cortex of FIV-infected cats neuroinflammation, loss of differentiated neurons (P < 0.01) and aberrant neuronal progenitor cell gene expression (P < 0.05) were observed. FIV envelope expression was detected in neural progenitor and monocytoid cells. GH treatment of FIV-infected animals induced insulin-like growth factor-1 expression in neurons (P < 0.01), enhanced neuronal survival (P < 0.01) and increased nestin expression (P < 0.05). Moreover, improved neurobehavioral performance (P < 0.01) and immunological status (P < 0.001) were observed, among GH-treated animals infected with FIV.
GH protects neural stem cells that are susceptible to lentivirus-mediated injury. Thus, GH may be a potential treatment for pediatric neuroAIDS because of its neurotrophic actions.
在儿童神经艾滋病模型中，研究人类免疫缺陷病毒1型（HIV-1）和猫免疫缺陷病毒（FIV）对神经干细胞活力的影响，以及生长激素（GH）的神经营养特性。
体外使用表达增强型绿色荧光蛋白的载体（SIN-EGFP）作为对照，用表达源自脑源性HIV-1毒株JR-FL包膜蛋白的辛德毕斯病毒载体（SIN-HIVenv）感染小鼠神经干细胞。评估生长激素处理后神经干细胞标志物的细胞存活情况及表达变化。新生猫感染具有神经毒性的FIV毒株，感染6周后用生长激素治疗6周。感染12周后，采用实时逆转录聚合酶链反应和免疫组织化学分析检测脑内神经祖细胞标志物表达、神经元丢失和神经炎症情况。
神经干细胞中HIV-1包膜表达降低了巢蛋白表达（P<0.05）并诱导细胞死亡（P<0.001），而生长激素可阻止这种情况。在FIV感染猫的额叶皮质中，观察到神经炎症、分化神经元丢失（P<0.01）和异常的神经祖细胞基因表达（P<0.05）。在神经祖细胞和单核细胞样细胞中检测到FIV包膜表达。对FIV感染动物进行生长激素治疗可诱导神经元中胰岛素样生长因子-1表达（P<0.01），提高神经元存活率（P<0.01）并增加巢蛋白表达（P<0.05）。此外，在接受生长激素治疗的FIV感染动物中，观察到神经行为表现改善（P<0.01）和免疫状态改善（P<0.001）。
生长激素可保护易受慢病毒介导损伤的神经干细胞。因此，由于其神经营养作用，生长激素可能是治疗儿童神经艾滋病的一种潜在疗法。
