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

人类疱疹病毒-6(HHV-6)被认为与B- 细胞性淋巴瘤和其他淋巴增生性疾病，尤其是 免疫抑制设置。该病毒(GS株)于#年首次分离。 1986年从艾滋病和其他淋巴增生性疾病患者那里获得。 为了阐明它在人类恶性肿瘤中的作用，我们研究了它 转变潜力。使用我们建立的基因检测系统 转移转化，我们首次报道了HHV-6基因组 (170kb，GS分离物)和两个亚基因组克隆pZVH14(8.7kb插入) PZVB70(21kb插入片段)可将NIH3T3细胞转化为 致瘤性。另外两株HHV-6分离株Z-29(CDC艾滋病分离株 患者)和GD(从慢性疲劳综合征分离出来)进行了测试 转换活动以了解它是否是 HHV-6。与GS分离物一样，GD和Z-29分离物的基因组DNA也是如此 将3T3细胞转化为致瘤性。限制性消化 Z-29株病毒DNA与GS或GD株有明显差异 GS和GD之间略有差异。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鉴定该基因 变换中涉及的序列以及是否有共同的变换 基因存在于这些分离株中。 我们还研究了HHV-6是否能将人类细胞转化为 确定其与人类恶性肿瘤的关系。我们发现， 可转化NIH的两个亚基因组克隆pZVH14和pZVB70 3T3细胞，也能转化成人的肿瘤 表皮角质形成细胞系(RHEK-1)。Southern杂交分析 提示pZVH14 DNA在转化和肿瘤中的存在 细胞。染色体分析确认这些肿瘤来自人类。 肿瘤细胞出现部分染色体异常。肿瘤被诊断为 组织学分析为低分化癌。进一步 正在进行的研究正在绘制转化基因的图谱并识别 转型的机制。

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.