Study of cells carrying HTLV-1 genes in HTLV-1 infected persons

人类DNA含有许多可垂直传播的逆转录病毒序列。哈曼T淋巴细胞病毒I型(HTLV-I)是一种可水平传播的逆转录病毒。HTLV-I与成人T细胞白血病(ATL)有关，但其病因尚不清楚。我们观察到癌症患者的HTLV-I血清阳性率高于健康人，这导致我们调查了人类组织中的HTLV-I基因(LTR、GAG和/或TAX)。血液和组织标本的DNA通过PCR-SSCP、直接测序和原位杂交(ISH)进行分析。用免疫组织化学方法检测基因产物的表达。鼻咽、泌尿生殖、骨和软组织、内分泌、呼吸道、造血、皮肤、生殖细胞、神经和胃肠道组织中HTLV-I相关序列阳性率分别为100%、92.3%、88.0%、87.5%、83.3%、76.5%、75.0%、71.4%、44.4%和33.3%。这些序列与HRES-1序列有变异突变，但没有同源性。信号…在肿瘤细胞和淋巴细胞中检测到较多的S。来自非肿瘤区的DNA也显示出信号，但放大倍数太低，无法进一步分析。ATL患者家族中血清阴性成员的DNA显示出与患者DNA不同的信号模式。此外，同一个体在不同时间检测到的HTLV-I基因多态性具有一定的变异性。在MNNG治疗后，携带原型LTR、GAG和TAX序列的淋巴细胞的姐妹染色单体交换频率明显高于不携带这些序列的淋巴细胞。在同时检测到HTLV-I和Epstein-Barr病毒基因的鼻咽癌中，观察到基因产物的异常表达。这些发现表明，HTLV-I相关序列存在于人类DNA中，当它们通过重排进化为原型序列时，会导致宿主细胞Upen暴露于包括病毒在内的致癌物时细胞基因的解除调控，从而导致宿主细胞DNA的不稳定性。(部分由日本教育、科学、体育和文化部科学研究补助金(C)提供支持。)较少

Human DNA harbors many vertically transmissible retroviral suquences. Haman T lymphotropic virus type I (HTLV-I) is a horizontally transmissible retrovirus. HTLV-I has been implicated in abult T cell leukemia (ATL), but its etiological rele remains unknown. Our observatons of a higher HTLV-I seroprevalence in cancer patients than in healthy persons led us to survey human tissues for HTLV-I genes (LTR,gag, and/or tax).DNA from blood and tissue specimens was analyzed by PCR-SSCP,direct sequencing, and in situ hybrodization (ISH). The gene product expression was examined by immunostaining. Chromosomal instability was tested by SCE.The ferquency of positivity for HTLV-I related sequences in tumors of nasopharynx, urogenital, bone and soft part, endocrine, respiratory, hematopoietic, skin, germ cell, neural, and gastrointestinal tissues was 100,92.3,88.0,87.5,83.3,76.5,75.0,71.4,44.4, and 33.3%, respectively. These sequences had variable mutations but no homology to HRES-1 sequences. Signal … More s were detected in tumor cells and lymphocytes. DNA from non-tumorous areas also showed signals but with too low amplification to analyze further. DNA from seronegative members of ATL patients'family showed signal patterns distinct from those seen in DNA of patients. Moreover, HTLV-I gene polymorphisms detected in same individuals at different times showed variability. Lymphocyes carrying prototype LTR,gag, and tax sequences showed SCE significantly higher than that of lymphocytes without these sequences when examined following MNNG treatment.The abnormal gene product expressio was observed in nasopharyngeal carcinomas in which genes of both HTLV-I and Epstein-Barr virus were detectable. These findings suggest that HTLV-I related sequences are present in human DNA and cause instability of host cell DNA when they evolve to prototype sequences through rearrangements leading to deregulation of cellulare genes of the host cell upen exposure to carcinogens including viruses. (Supported in part by Grant-in-Aid for Scientific Research (C) , The Ministry f Education, Science, Sports and Culture of Japan.) Less