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

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，它对仓鼠具有高度的神经致瘤性，被命名为JC病毒东京-1株(Abb：JCT)。JCT已被证明在仓鼠中不断地诱发小脑中部神经外胚层肿瘤，这与人类髓母细胞瘤非常相似。与美国和西德分离的JCT相比，JCT的宿主范围广，致瘤性很高。为了研究JCT的这一独特性质，我们克隆了JCT-DNA，并检测了DNA1的基因组特征。髓母细胞瘤来源：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，并用原位杂交法检测了接种后金黄地鼠小脑中的JCT mRNA。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首次检测到该基因的表达。因此，可以说发育中的外颗粒层的细胞感染了JCT，迁移到携带整合的JCT基因组的内颗粒层，然后在内颗粒层表达表型转化。JCT的限制性内切酶酶切图谱的差异：为了与其他国家的JCT进行比较，我们直接从原始PML脑和培养细胞中克隆了JCT DNA。JCT有两个分别被HincII和Pvu II酶切的裂解位点，这在其他菌株中没有描述。这对JCT来说，扩大宿主范围似乎是一种冒险。JCT株调控基因的差异：检测JCT株调控基因的DNA序列，并与其他JC病毒进行比较。JCT在TATA序列之后插入23个碱基对。在另一个中没有检测到的插入具有潜在的增强子核心序列。因此，JCT的高致瘤性可能是由于其调控基因中插入了增强子DNA。

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.