| Project/Area Number |
16390112
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
KOYANAGI Yoshio Kyoto University, Institutes for Virus Research, Professor, ウイルス研究所, 教授 (80215417)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2004: ¥9,100,000 (Direct Cost: ¥9,100,000)
|
|---|
| Keywords | HIV / HSV / Encephalitis / Brain / hippocampal slice culture / Neuronal differentiation / Macrophage / Microaray / 脳症 / 神経細胞破壊シグナル / マクロファージ / グリア細胞 / 海馬スライス培養 / HIV脳症 / 単純ヘルペス脳炎 |
|---|
| Research Abstract |
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.
|
