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Molecular mechanism of human herpesvirus 6 latent infector

Molecular mechanism of human herpesvirus 6 latent infector
人疱疹病毒6型潜伏感染者的分子机制
批准号:
09670316
负责人:
KONDO Kazuhiro
金额:
$1.92万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 1998

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中文摘要
翻译
人巨细胞病毒(CMV)是免疫功能低下个体和新生儿的重要病原体。人类疱疹病毒6型(humanherpesvirus 6,HHV-6)是一种可引起潜发性皮疹的病原体。这两种病毒属于b-疱疹病毒亚科。潜伏期是所有疱疹病毒的一个标志,对b型疱疹病毒的了解仍然很少。我们调查的维护和表达的病毒基因组在实验性潜伏感染使用粒细胞-巨噬细胞祖细胞(GM-Ps)的CMV和单核细胞/巨噬细胞的HHV-6。感染巨细胞病毒后,人GM-Ps携带病毒基因组,但不能支持生产性复制。为了更好地了解b型疱疹病毒潜伏期,我们研究了潜伏期系统中病毒基因的表达程度,发现了两类新的CMV潜伏期相关转录本(CLTs)和HHV-6潜伏期转录本(HHV-6LT)。我们表征了这些转录物,并且可以在来自健康CMV血清阳性成人的BM抽吸物和来自健康个体的HHV-6LT中检测到CLT。在CMV和HHV-6的情况下,病毒转录物都来自包含主要调控基因位点的区域;然而,它们的结构与生产期转录物显著不同。在CMV的情况下,这些转录本具有编码新的94和152 aa蛋白的潜力。在HHV-6中编码了新的99 aa、279 aa、91 aa和160 aa蛋白。因此,CMV和HHV-6的潜伏感染伴随着潜伏相关转录物的存在和免疫原性蛋白的表达。总之,这些结果表明,骨髓来源的髓系祖细胞是CMV潜伏期的重要天然部位,外周血来源的单核细胞/巨噬细胞对维持HHV-6潜伏期很重要。
英文摘要
Human cytomegalovirus (CMV) is a significant pathogen in immunocompromised individuals and neonates. Human herpesvirus 6 (HHV-6) is a causative agent of exanthem subitum. These two virusues belong to b-herpesvirus subfamily. Latency, a hallmark of all herpesvirus, remains poorly understood for b-herpesvirus. We investigate maintenance and expression of the viral genome in an experimental latent infection using granulocyte-macrophage progenitors (GM-Ps) for CMV and monocytes/macrophages for HHV-6. Following infection with cytomegalovirus, human GM-Ps carry the viral genome but fail to support productive replication. HHV-6 maintein its genome in human monocytes/macrophages.To better understand b-herpesvirus latency, we investigate the extent of viral gene expression in our latency system and found two novel classes of CMV latency associated transcripts (CLTs) and HHV-6 latency transcript (HHV-6LT). We characterize these transcripts and CLTs can be detected in BM aspirates from healthy CMV seropositive adults and HHV-6LT from healthy individuals. Both in the case of CMV and HHV-6, viral transcripts arise from a region encompassing the major regulatory gene locus ; however, their structure differs significantly from productive phase transcripts. In the case of CMV, these transcripts have the potential to encode novel 94 and 152aa proteins. In HHV-6 novel 99aa, 279aa, 91aa and 160aa proteins are encorded. Thus, latent infection by CMV and HHV-6 is accompanied by the presence of latency-associated transcripts and expression of immunogenic proteins. Overall, these results suggest that bone marrow-derived myeloid progenitors are an important natural site of CMV latency and peripheral blood derived monocytes/macrophages is important to maintein HHV-6 latency.
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会议论文
Aono T,et al.: "Monitoring of human cytomegalovirus infections in pediatric bone marrow transplant recipients by nucleic acid sequence-based amplification"J Infect Dis.. 178. 1244-1249 (1998)
Aono T 等人:“通过基于核酸序列的扩增来监测儿科骨髓移植受者中的人类巨细胞病毒感染”J Infect Dis. 178. 1244-1249 (1998)
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Aono T, et al.: "Monitoring of human cytomegalovirus infections in pediatric bone marrow transplant recipients by nucleic acid sequence-based amplification"J Infect Dis.. Nov;178(5). 1244-9 (1998)
Aono T 等人:“通过基于核酸序列的扩增来监测儿童骨髓移植受者中的人类巨细胞病毒感染”J Infect Dis. Nov;178(5)。
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Mori Y,et al.: "Analysis of human heroesvirus 6U3 gene,which is a positional homolog of human cytomegalovirus UL 24 gene."Vivology.. 249. 129-139 (1998)
Mori Y 等:“人类英雄病毒 6U3 基因的分析,该基因是人类巨细胞病毒 UL 24 基因的位置同源物。”Vivology.. 249. 129-139 (1998)
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共 7 条
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    • 项目类别:
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    • 资助金额:
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    • 财政年份:
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    Estimation of Speech Intelligibility using Automatic Speech Recognition
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    • 项目类别:
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    • 资助金额:
      $3.0万
    • 财政年份:
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    Fatigue and be-ta herpesvirus reactivation
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      19590483
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    • 财政年份:
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    Visualization and analysis of human herpesvirus 6 and 7 using their recombinant viruses
    • 批准号:
      17590422
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $2.24万
    • 财政年份:
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    • 负责人:
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    • 依托单位:
    国内基金
    海外基金
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