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

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生性疾病，特别是在 免疫抑制设置。 该病毒（GS株）首次分离于 1986年从艾滋病和其他淋巴组织增生性疾病患者身上。 为了阐明其在人类恶性肿瘤中的作用，我们研究了其在肿瘤中的作用。 转化潜力 利用我们建立的基因检测系统， 转移和转化，我们首次报道了HHV-6基因组 (170 kb，GS分离物）和两个亚基因组克隆pZVH 14（8.7kb插入物） pZVB 70（21 kb插入片段）可转化NIH 3 T3细胞， 致瘤性 另外两个HHV-6分离株Z-29（来自AIDS的CDC分离株 患者）和GD（从慢性疲劳综合征中分离）进行了测试， 转换活动，以了解它是否是一个共同的财产， HHV-6 与GS分离物一样，GD和Z-29分离物的基因组DNA也 转化3 T3细胞致瘤性。 限制性消化 病毒DNA表明Z-29与GS或GD有明显差异 分离物之间的差异，以及GS和GD之间的微小差异。 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 序列中涉及的转换和是否一个共同的转换 这些分离物中均存在gl基因。 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 同样的两个亚基因组克隆pZVH 14和pZVB 70可以转化NIH 3 T3细胞，也能够致瘤性转化人类 表皮角质形成细胞系（RHEK-1）。 Southern印迹分析 表明在转化的和肿瘤中存在pZVH 14 DNA 细胞 染色体分析确定肿瘤是人类起源的。 肿瘤细胞显示出一些染色体畸变。 肿瘤被诊断为 组织学分析为低分化癌。 进一步 研究正在进行中，以绘制转化基因，并确定 转化机制。

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.