Ensoli F, Ensoli B, Thiele C J
Cell and Molecular Biology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Virology. 1994 May 1;200(2):668-76. doi: 10.1006/viro.1994.1230.
Encephalopathy and neurological disorders are a major manifestation of pediatric AIDS. Although HIV-1 can replicate in cells of neuronal and glial origin, it is yet unclear whether immature neural cells, which are present during nervous system development, can support HIV-1 replication and whether neurotrophic factors can modulate HIV-1 gene expression. In this study we show that a glial cell line with a phenotype closely resembling immature glial cells is more permissive to HIV-1 infection and replication than a neuroblastic cell line. After HIV-1 infection or after transfection of these cells with the HIV-1 LTR-CAT reporter gene alone or in the presence of Tat, both HIV-1 replication and viral gene expression progressively decrease in the neuronal cell line, while they increase in the glial cell line. In both cell types viral gene expression and replication are augmented by the addition to the cells of nerve growth factor (NGF) at concentrations which induce neuronal differentiation. However, these effects are again more evident with the glial cell type, suggesting that immature glial cells may represent one of the major targets and reservoirs of HIV-1 in the developing nervous system. As NGF and Tat act synergistically in inducing HIV-1 gene expression, these data also suggest that during development the presence of high levels of neural trophic factors may activate viral replication and render the CNS more susceptible to the deleterious effects of HIV-1 infection.
脑病和神经障碍是儿童艾滋病的主要表现。尽管HIV-1可在神经元和神经胶质来源的细胞中复制，但尚不清楚神经系统发育过程中存在的未成熟神经细胞是否能支持HIV-1复制，以及神经营养因子是否能调节HIV-1基因表达。在本研究中，我们发现一种表型与未成熟神经胶质细胞非常相似的神经胶质细胞系比神经母细胞瘤细胞系对HIV-1感染和复制更敏感。在HIV-1感染后，或单独用HIV-1 LTR-CAT报告基因转染这些细胞，或在有Tat存在的情况下转染这些细胞后，HIV-1复制和病毒基因表达在神经元细胞系中逐渐降低，而在神经胶质细胞系中则增加。在两种细胞类型中，在诱导神经元分化的浓度下向细胞中添加神经生长因子（NGF）均可增强病毒基因表达和复制。然而，这些作用在神经胶质细胞类型中再次更为明显，这表明未成熟神经胶质细胞可能是发育中的神经系统中HIV-1的主要靶细胞和储存库之一。由于NGF和Tat在诱导HIV-1基因表达方面具有协同作用，这些数据还表明，在发育过程中高水平神经营养因子的存在可能激活病毒复制，并使中枢神经系统更容易受到HIV-1感染的有害影响。
