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Molecular mechanism of human herpesvirus 6 latent infection

人类疱疹病毒6型潜伏感染的分子机制

基本信息

批准号：
11670296
负责人：
KONDO Kazuhiro
金额：
$ 2.24万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

We have studied the latent and the productive infection of HHV-6 in the peripheral blood macrophages. As for the study on HHV-6 latency, four kinds of latency-associated transcripts of human herpesvirus 6 were identified, which were detected only in latently infected cells. Although they were encoded in the same direction as the immediate early (IE) 1/2 genes and shared their protein-coding region with IE1/2, their transcription start sites and exon(s) were latency-associated. Our findings revealed that the structures, the encoded proteins, and the expression of the HHV-6 latency-associated transcripts were similar to those of HCMV latency-specific transcripts. The H6LTs and the HCMV latency-specific transcripts may have some common function during latency. The conserved features of the HHV-6 and HCMV latent transcripts that we observed in this study may assist us in understanding β-herpesvirus latency further. As for the study on the acute infection, we investigated the tropism of HHV-6 in peripheral blood mononuclear cells (PBMCs) during acute infection. We detected 637 ± 273 copies of viral DNA in 10^4 MO/Mφ. In contrast, in 10^4CD4^+T cells, which have been reported to be viral carriers during the acute infection of HHV-6, we found only 115 ± 42 copies of viral DNA. Consistent with these data, virus was isolated from MO/Mφ an order of magnitude more frequently than from CD4^+ T cells. Viral mRNA U79/80, which indicates viral replication, was detectable in the MO/Mφ. In addition, the mRNAs that encode viral chemokine receptors U12 and U51, which may modify the function of MO/Mφ, were expressed in the cells. Therefore, productively infected MO/Mφ may be the dominant cell population that is responsible for HHV-6 viremia during acute HHV-6 infection. The strong interaction of HHV-6 with MO/Mφ may be partly responsible for the pathogenesis of this virus.

我们研究了HHV-6在外周血巨噬细胞中的潜伏性和生产性感染。在HHV-6潜伏期的研究中，鉴定了4种人类疱疹病毒6型潜伏相关转录物，仅在潜伏感染的细胞中检测到。虽然它们与立即早期（IE）1/2基因编码方向相同，并与IE 1/2共享其蛋白编码区，但它们的转录起始位点和外显子与潜伏期相关。我们的研究结果表明，HHV-6潜伏相关转录本的结构，编码的蛋白质和表达与HCMV潜伏特异性转录本相似。H6LTs和HCMV潜伏期特异性转录本在潜伏期可能有一些共同的功能。我们在本研究中观察到的HHV-6和HCMV潜伏转录本的保守特征可能有助于我们进一步了解β-疱疹病毒的潜伏期。在急性感染的研究方面，我们研究了HHV-6在急性感染时外周血单个核细胞（PBMCs）中的嗜性。我们在10^4 MO/M φ中检测到637 ± 273个病毒DNA拷贝。相比之下，在10^4CD4 ^+ T细胞中，我们只发现了115 ± 42个病毒DNA拷贝。与这些数据一致，从MO/M φ中分离出病毒的频率比从CD4 ^+ T细胞中高一个数量级。在MO/M φ中可检测到病毒mRNA U79/80，其指示病毒复制。此外，在细胞中表达了编码病毒趋化因子受体U12和U51的mRNA，它们可能改变MO/M φ的功能。因此，在急性HHV-6感染期间，生产性感染的MO/M φ可能是导致HHV-6病毒血症的主要细胞群。HHV-6与MO/M φ的强相互作用可能是HHV-6致病的部分原因。