CYTOMEGALOVIRUS AND HUMAN MALIGNANCY

本项目的总体目标是通过以下方式研究该机制： 人巨细胞病毒（CMV）与其宿主相互作用， 与其他感染因子一起导致恶性转化 人类细胞。 工作重点将放在共同研究上， CMV在人类恶性肿瘤中的病因学作用 的假设 本研究通过对CMV形态转化体DNA 单靠地铁不足以启动转型 人类细胞。 它可能需要反式激活因子， 从CMV立即早期（IE）基因1和2的表达， 反式激活基因 此外，还假设， CMV IE基因产物能够促进转化， 由其它病毒因子诱导的人细胞，如人 乳头瘤病毒（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） 确定了人CMV IE基因的反式激活区， 能够反式激活人免疫缺陷病毒LTR启动子 病毒和启动子的早期和膜抗原 EB病毒 (2)为了研究反式激活是否 CMV IE基因1和2以及CMV mtr DNA（IE基因4）可 反式激活细胞ras癌基因表达， 转化成细胞，反之亦然。 (3)调查是否 CMV IE基因能提高CMV的转化效率 mtr DNA片段（HindIII A-BamH 1 J）或HPV 16和18型 人成纤维细胞和宫颈上皮细胞中的DNA。 (4)到 检查感染性CMV或CMV IE基因1和2是否可以 反式激活HPV 16和型的表达和复制 18在人体细胞中 (5)建立检测CMV的初步研究 DNA和HPV DNA序列、病毒mRNA和癌基因 在宫颈癌中的表达， 宫颈癌的病因学作用。 (6)检测CMV相关 DNA和mRNA序列，和细胞癌基因表达， Kaposi肉瘤，并分析统计学意义 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.