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Investigation of tissue destruction signals on viral encephalitis

Investigation of tissue destruction signals on viral encephalitis
病毒性脑炎组织破坏信号的研究
批准号:
16390112
负责人:
KOYANAGI Yoshio
金额:
$9.6万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2004
资助国家:
日本
项目状态:
已结题
起止时间:
2004 至 2005

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中文摘要
翻译
为了解决HIV和HSV脑炎的病理机制,特别是关于脑中的组织破坏信号,我们建立了大鼠海马切片培养,其中组织学神经元结构保持不变,并检查病毒在该培养物中复制的动力学。虽然发现HSV-1感染的大规模传播和严重的组织损伤,但病毒能够驻留在一些未成熟的细胞中并由其产生,可能是神经干细胞,这表明神经干细胞是脑组织中持续和活动性感染的主要靶点之一。巨噬细胞似乎是脑组织中被HIV-1感染的关键细胞类型之一。研究表明,感染HIV-1的巨噬细胞侵入脑组织并释放一些因子,对神经元造成损伤。尽管切片培养物对HIV-1不敏感,但在HIV-1感染的人巨噬细胞存在下,某些神经元的培养条件和神经元祖细胞的分化能力似乎受到显著干扰,这可能产生神经毒性因子和神经元分化抑制因子。然后,将HSV-1和HIV-1感染的样品用于微阵列分析,以找到影响病毒发病机制的特异性信号分子。目前,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病毒在CNS中的发病机制。
英文摘要
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.
期刊论文(36)
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会议论文
Potent Anti-R5-human immunodeficiency virus type leffects of a CCR5 antagonist, AK602/ON04128/GW873140, in a novel human peripheral blood mononuclear cell nonobese diabetic-SCID, interleukin 2 receptor γ-chain-knocked-out AIDS mouse model.
CCR5 拮抗剂 AK602/ON04128/GW873140 在新型人外周血单核细胞非肥胖糖尿病 SCID、白细胞介素 2 受体 γ 链敲除 AIDS 小鼠模型中的强效抗 R5 人类免疫缺陷病毒类型。
DOI: --
发表时间: 2005
期刊: Journal of Virology 79
影响因子: --
作者: [Nakata H, et al.]
通讯作者: et al.
A lentiviral cDNA library employing lambda recombination used to clone an inhibitor of human immunodeficiency virus type l-induced cell death
采用 lambda 重组的慢病毒 cDNA 文库,用于克隆人类免疫缺陷病毒 L 型诱导细胞死亡的抑制剂
DOI: --
发表时间: 2004
期刊: Journal of Virology 78
影响因子: --
作者: [Kawano Y, Koyanagi Y et al.]
通讯作者: Koyanagi Y et al.
DOI: 10.1182/blood-2005-02-0536
发表时间: 2005-11-15
期刊: BLOOD
影响因子: 20.3
作者: [Munakata, Y, Saito-Ito, T, Sasaki, T]
通讯作者: Sasaki, T
DOI: 10.1128/jvi.79.4.2087-2096.2005
发表时间: 2005-02-01
期刊: JOURNAL OF VIROLOGY
影响因子: 5.4
作者: [Nakata, H, Maeda, K, Mitsuya, H]
通讯作者: Mitsuya, H
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