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Investigation of the genes associated with tumorigenicity of Marek's disease virus.

研究与马立克氏病病毒致瘤性相关的基因。

基本信息

批准号：
02660301
负责人：
HAYASHI Masanobu
金额：
$ 1.22万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1991
项目状态：
已结题

项目摘要

Marek's disease virus (MDV) is an avian herpesvirus which induces lymphoproliferative disease in chickens. It has been suggested that maintenance of tumorigenicity might be associated with the expression of the 1.8 kb gene from 6amHI-H region of MDV DNA. However, direct proof of the function of the 1.8 kb gene has been lacking. We examined the role of the 1.8 kb gene in tumorigenicity, using oligonucleotides complementary to the 1.8 kb gene. Although maintenance of latent infection of MDV seems to involve mechanisms regulating viral transcription, it is not clear which factors are responsible for transcriptional control. We investigated whether primary and higher order structures of MDV DNA are correlated with the repression of transcription from MDV genome in lymphoblastoid cell lines.1. An oligonucleotide complementary to the splice donor sequence of the 1.8 kb gene produced from 6amHI-H region of MDV DNA inhibited the proliferation of lymphoblastoid cell line. MDCC-MSBI(MSBI). but not that of the avian lymphoid leukosis-derived lymphoblastoid cell line, LSCC-BK3. Colony formation in soft agar was also inhibited by treatment of MSBI cells with antisense oligonucleotide. Thus. expression of the 1.8 kb gene family is directly associated with maintenance of tumorigenic state of transformed MDV-derived lymphoblastoid cells.2. The unique fragment flanking the region which contains the putative replication origin of MDV DNA was found in only MDV DNA from virus-nonproducing cell iine MDCC-RPI (RPI). The change in DNA structure near the region of replication origin might be associated with the loss of MDV productivity in RPI. The latent MDV genome are folded into nucleosomal structures in MSBI and RPI. There was no difference between transcriptionally active and inactive regions of MDV genome with regard to nucleosomal patterns.

马立克氏病病毒（MDV）是一种禽疱疹病毒，可引起鸡淋巴组织增生性疾病。有人提出，致瘤性的维持可能与 MDV DNA 6amHI-H 区域的 1.8 kb 基因的表达有关。然而，目前还缺乏 1.8 kb 基因功能的直接证据。我们使用与 1.8 kb 基因互补的寡核苷酸检查了 1.8 kb 基因在致瘤性中的作用。尽管MDV潜伏感染的维持似乎涉及调节病毒转录的机制，但尚不清楚哪些因素负责转录控制。我们研究了MDV DNA 的一级和高级结构是否与淋巴母细胞系中MDV 基因组的转录抑制相关。1．与 MDV DNA 6amHI-H 区域产生的 1.8 kb 基因剪接供体序列互补的寡核苷酸抑制类淋巴母细胞系的增殖。 MDCC-MSBI（MSBI）。但不是禽类淋巴白血病来源的淋巴母细胞系 LSCC-BK3 的细胞。用反义寡核苷酸处理 MSBI 细胞也可抑制软琼脂中的集落形成。因此。 1.8 kb基因家族的表达与转化的MDV源性淋巴母细胞致瘤状态的维持直接相关。2．仅在来自不产生病毒的细胞系 MDCC-RPI (RPI) 的 MDV DNA 中发现了包含 MDV DNA 推定复制起点的区域侧翼的独特片段。复制起点区域附近 DNA 结构的变化可能与 RPI 中 MDV 生产力的损失有关。潜在的 MDV 基因组在 MSBI 和 RPI 中折叠成核小体结构。 MDV 基因组的转录活性区域和非活性区域在核小体模式方面没有差异。