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Visualization and analysis of human herpesvirus 6 and 7 using their recombinant viruses

使用重组病毒对人类疱疹病毒 6 型和 7 型进行可视化和分析

基本信息

批准号：
17590422
负责人：
KONDO Kazuhiro
金额：
$ 2.24万
依托单位：
Jikei University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590422/
关键词：
human herpesvirus 6 human herpesvirus 7 HHV-6 HHV-7 SCID-hu mouse stress fatigue

项目摘要

1. Visualization of viral latency and reactivationTo visualize the viral reactivation of human herpesvirus (HHV)-6 and HHV-7, we planned to identify the viral early gene promoters that were activated during viral reactivation and viral replication. Then, we have analyzed the character of early gene promoters, such as p41, DNA pol, U41 and U79/80. As a result, these viral early gene promoters were activated mainly by immediate early (IE) 2, and IE2 strongly activate the early gene promoters with IE1 synergistically. In the U79/80 gene promoter region, we identified the cis repression sequence (CRS) like motif that was reported in human cytomegalovirus immediate early and very early gene promoter region. These findings suggest that U79/80 gene promoter is a suitable promoter that can respond to the early stage of HHV-6 reactivation or replication.2. Establishment of HHV-6 latency/reactivation system using SCID-hu mouseTo investigate the molecular mechanism of HHV-6 and HHV-7 latency, we have established their latent infection system by using non-obese diabetic-severe combined immunodeficiency (NOD-SCID)-hu mouse. We have transplanted umbilical cord blood cells into NOD-SCID mouse, and infected wild type HHV-6 or recombinant HHV-6 expressing enhanced green fluorescent protein (EGFP). In this latency system, we have observed that approximately 100 fold number of cells had HHV-6 DNA than in the human samples. Then we have studied the form of HHV-6 DNA in this latent system, and found that it showed the circular form. These findings suggest that the HHV-6 latent system using NOD-SCID-hu mouse is useful tool for investigating HHV-6 latency and reactivation.

1.病毒潜伏和重新激活的可视化为了可视化人类疱疹病毒（HHV）-6和HHV-7的病毒重新激活，我们计划鉴定在病毒重新激活和病毒复制过程中被激活的病毒早期基因启动子。然后，我们分析了早期基因启动子的特征，如p41、DNA pol、U41和U79/80。结果，这些病毒早期基因启动子主要由立即早期（IE）2激活，IE2与IE1协同强烈激活早期基因启动子。在U79/80基因启动子区域，我们鉴定了在人巨细胞病毒立即早期和极早期基因启动子区域中报道的顺式抑制序列（CRS）样基序。这些结果表明U79/80基因启动子是一个合适的启动子，可以响应HHV-6重新激活或复制的早期阶段。2．利用SCID-hu小鼠建立HHV-6潜伏/再激活系统为了研究HHV-6和HHV-7潜伏的分子机制，我们利用非肥胖糖尿病-严重联合免疫缺陷(NOD-SCID)-hu小鼠建立了它们的潜伏感染系统。我们将脐带血细胞移植到NOD-SCID小鼠体内，并感染野生型HHV-6或表达增强型绿色荧光蛋白（EGFP）的重组HHV-6。在这个潜伏系统中，我们观察到含有 HHV-6 DNA 的细胞数量大约是人类样本的 100 倍。然后我们研究了该潜在系统中HHV-6 DNA的形态，发现其呈环状。这些发现表明，使用 NOD-SCID-hu 小鼠的 HHV-6 潜伏系统是研究 HHV-6 潜伏和重新激活的有用工具。