Herpesviral Gene Expression in Kaposis Sarcoma

卡波济肉瘤中的疱疹病毒基因表达

• 批准号: 6779787
• 负责人: DON GANEM
• 金额: $ 27.55万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6779787
• 关键词: Kaposi' s sarcoma; athymic mouse; cyclins; gene expression; gene targeting; genetic transcription; genetically modified animals; human herpesvirus 8; latent virus infection; lymphoma; neoplasm /cancer epidemiology; nuclear factor kappa beta; protein structure function; ribonucleoproteins; vascular endothelium; virus genetics; virus protein; virus replication

Infection by Kaposi's sarcoma-associated herpesvirus (KSHV; also called human herpesvirus 8) is a key factor in the development of Kaposi's sarcoma (KS), a proliferative lesion of endothelial cells that until recently was the commonest neoplasm of AIDS patients. In KS tumors, the viral genome resides within the majority of spindle cells in a latent state; smaller numbers of tumor cells display lytic infection. This grant began with the examination of viral gene expression in KS tumors, identifying several latent and lytic genes expressed in that context. The present renewal application seeks to further characterize the expression and function of these genes. Specifically, we will (i) develop an endothelial cell culture model of KSHV latency and use it to develop a genetic system for the creation and analysis of mutant KSHV genomes; (ii) characterize the phenotypic consequences of expression of a major KSHV latency locus encoding orfs 71,72 and 73; (iii) further explore the mechanisms and consequences of constitutive signaling by the KSHV K1 protein; (iv) characterize the biochemical activities and interactions of the KSHV kaposin gene products; and (v) identify the constituents of an abundant viral ribonucleoprotein complex and determine their function.

Kaposi的肉瘤相关疱疹病毒（KSHV；也称为人疱疹病毒8）是Kaposi肉瘤（KS）发展的关键因素，Kaposi的肉瘤（KS）是内皮细胞的增殖性病变，直到最近，这是AIDS患者最常见的Neoplasm Neoplasm。在KS肿瘤中，病毒基因组位于潜在状态的大多数纺锤体内。较少数量的肿瘤细胞显示裂解感染。这项赠款始于对KS肿瘤中病毒基因表达的检查，确定了在这种情况下表达的几种潜在和裂解基因。目前的更新应用旨在进一步表征这些基因的表达和功能。具体而言，我们将（i）开发一个KSHV潜伏期的内皮细胞培养模型，并使用它来开发一种遗传系统来创建和分析突变的KSHV基因组； （ii）表征编码ORF的主要KSHV潜伏期基因座的表达后果71,72和73； （iii）进一步探讨了KSHV K1蛋白的本构信号传导的机制和后果； （iv）表征KSHV Kaposin基因产物的生化活性和相互作用； （v）确定丰富的病毒核糖核蛋白复合物的成分并确定其功能。