ONCOGENIC POTENTIAL OF HUMAN HERPESVIRUS-6 (HHV-6)

人类疱疹病毒 6 (HHV-6) 的致癌潜力

• 批准号: 3792525
• 负责人: A RAZZAQUE
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3792525
• 关键词: 3T3 cells; AIDS; cell transformation; chromosome aberrations; chronic fatigue syndrome; genetic strain; genome; histology; histopathology; human herpesvirus 6; human tissue; lymphoma; molecular cloning; neoplasm /cancer diagnosis; neoplastic transformation; nucleic acid sequence; oncogenic virus; opportunistic infections; restriction mapping; southern blotting; transfection; transforming virus; viral carcinogenesis; virus DNA; virus genetics; virus protein

Human herpesvirus-6 (HHV-6) has been proposed to be associated with B- cell lymphoma and other lymphoproliferative disorders especially in immunosuppressed settings. The virus (GS strain) was first isolated in 1986 from patients with AIDS and other lymphoproliferative disorders. To elucidate its role in human malignancies, we examined its transforming potential. Using our established assay system for gene transfer and transformation, we first reported that HHV-6 genome (170 kb, GS isolate) and two subgenomic clones pZVH14 (8.7 kb insert) and pZVB70 (21 kb insert) could transform NIH 3T3 cells to tumorigenicity. Two other HHV-6 isolates, Z-29 (CDC isolate from AIDS patient) and GD (isolated from chronic fatigue syndrome) were tested for transforming activity to understand whether it is a common property with HHV-6. Like GS isolate, genomic DNAs of GD and Z-29 isolates also transformed 3T3 cells to tumorigenicity. Restriction digestion of the viral DNAs indicated distinct difference between Z-29 and GS or GD isolates and a minor difference between GS and GD. Z-29 DNA seemed to be more tumorigenic than GS or GD DNA. We are currently performing the molecular biological analysis of the tumors to identify the gene sequences involved in transformation and whether a common transforming gene exists in these isolates. We also investigated whether HHV-6 can transform human cells to establish its relationship to human malignancies. We found that the same two subgenomic clones pZVH14 and pZVB70 that could transform NIH 3T3 cells, were also capable of tumorigenic conversion of human epidermal keratinocyte cell line (RHEK-1). Southern blot analysis indicated the presence of pZVH14 DNAs in the transformed and tumor cells. Chromosome analysis identified the tumors to be of human origin. Tumor cells showed some chromosomal aberrations. Tumors were diagnosed as poorly differentiated carcinomas by histological analysis. Further studies are in progress to map the transforming genes and to identify the mechanism of transformation.

人类疱疹病毒 6 (HHV-6) 被认为与 B- 细胞淋巴瘤和其他淋巴增殖性疾病，尤其是 免疫抑制环境。 该病毒（GS 株）首次分离于 1986年来自艾滋病和其他淋巴组织增生性疾病患者。 为了阐明其在人类恶性肿瘤中的作用，我们研究了其 转化潜力。 使用我们建立的基因检测系统 转移和转化，我们首先报道了HHV-6基因组 （170 kb，GS 分离物）和两个亚基因组克隆 pZVH14（8.7 kb 插入片段） pZVB70（21 kb 插入片段）可以将 NIH 3T3 细胞转化为 致瘤性。 另外两种 HHV-6 分离株，Z-29（CDC 从 AIDS 中分离株 患者）和 GD（从慢性疲劳综合症中分离出来）进行了检测 转变活动以了解它是否是共同财产 HHV-6。 与 GS 分离株一样，GD 和 Z-29 分离株的基因组 DNA 也 将3T3细胞转化为致瘤性。 限制性消化 病毒 DNA 显示 Z-29 和 GS 或 GD 之间存在明显差异 分离株，GS 和 GD 之间存在微小差异。 Z-29 DNA 似乎 比 GS 或 GD DNA 更具致瘤性。 我们目前正在执行 对肿瘤进行分子生物学分析以确定基因 参与转化的序列以及是否有共同的转化 基因存在于这些分离株中。 我们还研究了 HHV-6 是否可以将人类细胞转化为 确定其与人类恶性肿瘤的关系。 我们发现 相同的两个亚基因组克隆 pZVH14 和 pZVB70 可以转化 NIH 3T3细胞也能够将人类的 表皮角质形成细胞系（RHEK-1）。 Southern印迹分析 表明转化体和肿瘤中存在 pZVH14 DNA 细胞。 染色体分析确定肿瘤源自人类。 肿瘤细胞表现出一些染色体畸变。 确诊为肿瘤 通过组织学分析为低分化癌。 更远 正在进行研究以绘制转化基因图谱并确定 转化机制。