Investigation of tissue destruction signals on viral encephalitis

为了解决HIV和HSV脑炎的病理机制，特别是关于脑内组织破坏信号，我们建立了保持组织神经元结构的大鼠海马片培养，并检测了该培养物中病毒复制的动力学。尽管发现了HSV-1感染的大量传播和严重的组织损伤，但该病毒能够在一些未成熟的细胞中生存并产生，可能是神经干细胞，这表明神经干细胞是脑组织持续和活跃感染的主要靶点之一。巨噬细胞似乎是脑组织中感染HIV-1的关键细胞类型之一。已有研究表明，感染HIV-1的巨噬细胞可以侵入大脑，释放一些对神经元有损伤作用的因子。虽然切片培养对HIV-1不敏感，但在HIV-1感染的人巨噬细胞存在下，部分神经元的培养条件和神经前体细胞的分化能力明显受到干扰，可能产生神经毒性因子和神经元分化抑制因子。然后，对HSV-1和HIV-1感染的样本进行微阵列分析，以寻找影响病毒致病的特定信号分子。到目前为止，已经发现了许多候选细胞分子，并通过RNA-PCR分析证实了其表达的变化。这些数据表明，脑源性宿主因子有助于增强中枢神经系统中病毒的致病作用。

To solve the pathological mechanism of HIV and HSV encephalitis, especially regarding the tissue destruction signals in brain, we established a rat hippocampal slice culture in which histological neuronal structure is maintained and examined the dynamics of virus replication in this culture. Although massive dissemination of HSV-1 infection and severe tissue damage was found, the virus is able to reside in and be produced from some immature cells, probably neuronal stem cells, suggesting that neuronal stem cell is one of the major targets for persistent and active infection in brain tissues. Macrophages appear to be one of the key cell types that are infected by HIV-1 within brain tissue. It has been shown that macrophages infected with HIV-1 invade to brain and release some factors which provide damage to neurons. Although the slice culture was not susceptible to HIV-1, culture condition of some neurons and differentiation ability of neuronal progenitors appeared to be significantly disturbed in the presence of HIV-1-infected human macrophages, probably which may produce neurotoxic factors and neuronal differentiation inhibition factor. Then, both HSV-1- and HIV-1-infected samples were applied for microarray analysis to find specific signal molecules influencing viral pathogenesis. So far, many candidate cellular molecules were found and the alternations of its expression were confirmed from RNA-PCR analysis. These data suggest that brain-derived host factors contribute to augmentation of virus pathogenesis in CNS.