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Mechanism of neurooncogenesis by JC virus -- Relationship to human brain tumors.

JC 病毒的神经肿瘤发生机制——与人脑肿瘤的关系。

基本信息

批准号：
59480148
负责人：
NAGASHIMA Kazuo
金额：
$ 3.14万
依托单位：
Hokkaido University (1986)The University of Tokyo (1984-1985)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1984
资助国家：
日本
起止时间：
1984 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-59480148/
关键词：
JC virus Medulloblastoma Molecular cloning in situ hybridization restriction enzyme cleavage Regulatory gene エンハンサー

项目摘要

A new human polyomavirus, JC virus, first isolated in Japan by us, has been shown to be highly neurooncogenic to hamsters, and was named JC virus Tokyo-1 strain (Abb: JCT). JCT has been shown to induce constantly mid-cerebellar neuroectodermal tumors in hamsters, which are very similar to human medulloblastoma. The host range of JCT was wide, and tumorgeniciy was very high, compared to those isolated from U.S.A. and West Germany. To investigate this unique properties of JCT, we cloned JCT-DNA, and examined the genomic characters of DNA.1. Origin of medulloblastoma: We cloned the T region of JCT-DNA, and labeled the antisence mRNA of JCT-T region with radioisotope, and examined JCT mRNA in the hamster cerebellum after inoculation by in situ hybridization. The mRNA was first detected in the cells of the cerebellar molecular layer between the external granular layer and the internal granular layer, as well as cells in the internal granular layer. Thus, it could be said that the cells in the developing external granular layer were infected with JCT, migrated into the internal granular layer carrying the integrated JCT genome, then express the phenotypic transformation in the internal granular layer.2. Difference of JCT in restriction enzyme cleavaged pattern: To compare the JCT to those from other countries, we cloned JCT DNA directly from the original PML brain as well as cultured cells. JCT has two cleavaged sites by Hinc II and Pvu II digestion, repectively, which were not described in the other strains. This seemed to be adventagious for JCT to widen the host range.3. Differences of regulatory gene of JCT: We examined the DNA sequences of the regulatory genes of JCT, and compared them with other JC viruses. JCT has 23-base pair insertion after TATA sequences. The insertion, which has not detected in the other , has a potential core sequence of the enhancer. Thus, the high oncogenicity of JCT may owe this insertion of enhancer DNA in its regulatory gene.

JC病毒是我们在日本首次分离到的一种新的人类多瘤病毒，对仓鼠具有高度的神经致瘤性，被命名为JC病毒东京1株（简称：JCT）。JCT已被证明在仓鼠中持续诱导小脑中神经外胚层肿瘤，其非常类似于人类髓母细胞瘤。与美国和德国分离株相比，JCT的宿主范围广，致瘤性高。为了研究JCT的这种独特性质，我们克隆了JCT-DNA，并检查了DNA的基因组特征。髓母细胞瘤的起源：我们克隆了JCT-DNA的T区，用放射性同位素标记了JCT-T区的反义mRNA，用原位杂交技术检测了接种后金黄地鼠小脑中JCTmRNA的表达。该mRNA首先在小脑外颗粒层和内颗粒层之间的分子层细胞以及内颗粒层细胞中检测到。因此，可以说发育中的外颗粒层细胞感染了JCT，携带整合的JCT基因组迁移到内颗粒层，然后在内颗粒层表达表型转化. JCT在限制性内切酶切割模式上的差异：为了将JCT与其他国家的JCT进行比较，我们直接从原始PML脑以及培养细胞中克隆了JCT DNA。JCT有两个被Hinc II和Pvu II消化的切割位点，这在其他菌株中没有描述。这似乎是冒险的JCT扩大主机范围。JCT病毒调控基因的差异：我们对JCT病毒调控基因的DNA序列进行了分析，并与其它JC病毒进行了比较。JCT在TATA序列之后具有23个碱基对插入。在另一个中未检测到的插入具有增强子的潜在核心序列。因此，JCT的高致瘤性可能是由于在其调节基因中插入了增强子DNA。