Studies on a mechanism of hantavirus persistent infection in central nervous system and immune system

汉坦病毒持续感染中枢神经系统和免疫系统机制研究

基本信息

批准号：
10306019
负责人：
ARIKAWA Jiro
金额：
$ 22.78万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10306019/
关键词：
Hemorrhagic fever with renal syndrome HFRS hantavirus zoonosis virus infection pathogenicity genetic reassortant infection enhancement

项目摘要

1. Hantavirus infection was enhanced about 10 times by addition of lectins (DBA and SBA) which specifically bind to N-acetylgalactosamine. This enhancement was considered to caused by the cross linking between receptor to virion by the lectins.2. Two Vero E6 cell subclones, one induce low pH dependent cell fusion after hantavirus infection and the other resistant to cause cell fusion, were established. By using the two cell clones, the possible role for the cellular factor for responsible for induce infected cell fusion was considered.3. After peripheral infection of hantavirus to mice, virulent virus reached to brain 4 to 5 days earlier than that of avirulent virus. This difference was considered as a mechanism which define the virulence of hantavirus in the mouse model.4. Virulent hantavirus showed higher growth rate in the brain micro vascular cells and peritoneal macrophage, suggesting that virulence relates to the growth ability in the target organs.5. Genetic reassortant virus between virulent and avirulent viruses were established. The comparison of the virulence of the reassortant viruses indicated that one amino acid difference at enveloped protein and nucleotide difference in the polymerase gene are related to the virulence.6. Virulent hantavirus infected SCID mice were passively transferred with spleen cells of immunized BALB/c mice 3 weeks after infection. The recipient SCID mice represented apparent weight loss 4 days after the transfer, indicating the immune mediated pathogenicity.7. Hantaan virus S and M genome segment which encoding nucleocapsid protein and enveloped glycoprotein, respectively were cloned and expressed in the mammalian cells.8. Entire L genome segment which encodes polymerase was cloned. The expression of the L clone is under going.

1。通过添加凝集素（DBA和SBA），汉塔病毒感染增强了约10倍，该凝集素（DBA和SBA）特别结合了N-乙酰基乳糖胺。这种增强被认为是由凝集素与病毒体之间的交叉连接引起的。2。建立了两个Vero E6细胞亚克隆，一种诱导汉坦病毒感染后低pH依赖性细胞融合，另一种抗性引起细胞融合的抗性。通过使用两个细胞克隆，考虑了诱导感染细胞融合的细胞因子的可能作用。3。汉坦病毒对小鼠的周围感染后，毒性病毒比无毒病毒早4至5天。这种差异被认为是定义小鼠模型中汉坦病毒的毒力的机制。4。毒性汉坦病毒在脑微血管细胞和腹膜巨噬细胞中显示出较高的生长速率，这表明毒力与靶器官的生长能力有关。5。建立了毒和无毒病毒之间的遗传重新分类病毒。重新成分病毒的毒力的比较表明，聚合酶基因中包膜蛋白和核苷酸差异的一个氨基酸差异与毒力有关。6。感染后3周，用免疫的BALB/c小鼠的脾脏细胞被动地转移了毒力的汉坦病毒感染小鼠。受体SCID小鼠在转移后4天表示显而易见的体重减轻，表明免疫介导的致病性7。汉坦病毒S和M基因组段分别克隆并在哺乳动物细胞中克隆并表达了分别编码核素蛋白和包裹的糖蛋白。8。克隆编码聚合酶的整个L基因组段。 L克隆的表达正在进行中。