CYTOMEGALOVIRUS AND HUMAN MALIGNANCY

这个项目的总体目标是通过以下方式研究这一机制 哪种人类巨细胞病毒(CMV)与其宿主或 与其他感染源一起导致恶变 人类细胞的。努力将重点放在共同研究上。 巨细胞病毒在人类恶性肿瘤中的病因学作用。的假说 本研究是对CMV的DNA进行形态转化 仅有区域(MTR)不足以启动转型 人类细胞的。它可能需要提供反式激活因子 从CMV即刻早期(IE)基因1和2的表达来看， 反式激活基因。此外，还假设 CMV IE基因产物能促进细胞转化 由其他病毒剂诱导的人类细胞，如人类 乳头状瘤病毒(HPV)。方法包括使用重组 DNA技术和其他分子生物学技术 在分子水平上研究以下具体目标：(1) 确定人巨细胞病毒IE基因的反式活化区 能够反式激活人类免疫缺陷的LTR启动子 一种早期和一种膜抗原的病毒启动子 爱泼斯坦—巴尔病毒。(2)调查反式激活是否 CMV IE基因1和2以及CMV MTR DNA(IE基因4)可以 反式激活细胞ras癌基因表达，进而导致 细胞转化，反之亦然。(三)调查是否 CMV IE基因可提高CMV的转化效率 MTR DNA片段(HindIII A-BamH1J)，或HPV 16和18型 人成纤维细胞和宫颈上皮细胞中的脱氧核糖核酸S。(4)至 检测传染性巨细胞病毒或巨细胞病毒IE基因1和2是否可以 反式激活HPV16和HPV16型的表达和复制 18在人类细胞中。(5)建立检测巨细胞病毒的先导研究 DNA和HPV DNA序列、病毒信使核糖核酸和癌基因 宫颈癌组织中表达的研究可能存在的问题 宫颈癌的病因学作用。(6)检测CMV相关病毒 DNA和mRNA序列与细胞癌基因表达的关系 Kaposi肉瘤，并分析其统计学意义 这些数据。

The overall objective of this project is to study the mechanism by which human cytomegalovirus (CMV) interacts with its host or with other infectious agents to result in malignant transformation of human cells. Efforts will be focused on the study of the co- etiological role of CMV in human malignancies. The hypothesis of this study is that the DNA of CMV morphological transforming region (mtr) alone is not sufficient to initiate the transformation of human cells. It may require transactivating factors provided from the expression of CMV immediate-early (IE) gene 1 and 2, transactivating gene. In addition, it is also hypothesized that CMV IE gene products are able to promote the transformation of human cells induced by other viral agents, such as human papilloma virus (HPV). Approaches include using recombinant DNA technology and other molecular biology techniques to investigate at molecular level the following specific aims: (1) To define the transactivating region of human CMV IE gene which is able to transactivate LTR promoter of human immunodeficiency virus and promoters of an early and a membrane antigens of Epstein-Barr virus. (2) To investigate whether transactivating CMV IE gene 1 and 2, and CMV mtr DNA (IE gene 4) can transactivate cellular ras oncogene expression which in turn leads to cell transformation, or vice versa. (3) To investigate whether CMV IE gene can promote the transforming efficiencies of CMV mtr DNA fragment (HindIII A-BamH1J), or HPV type 16 and 18 DNA s in human fibroblasts and cervical epithelial cells. (4) To examine whether infectious CMV or CMV IE gene 1 and 2 can transactivate the expression and replication of HPV 16 and type 18 in human cells. (5) To establish a pilot study to detect CMV DNA and HPV DNA sequences, viral mRNA's and oncogenes expression in cervical cancers for studying there possible etiological role in cervical cancer. (6) To detect CMV related DNA and mRNA sequences, and cellular oncogene expression in Kaposi's sarcoma, and to analyze the statistical significance of these data.