HERPESVIRAL GENE EXPRESSION IN KAPOSIS SARCOMA

卡波西斯肉瘤中疱疹病毒基因的表达

• 批准号: 2769924
• 负责人: DON GANEM
• 金额: $ 21.69万
• 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 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769924
• 关键词: AIDS; HIV infections; Kaposi's sarcoma; disease /disorder proneness /risk; gene expression; human herpesvirus 8; molecular cloning; molecular pathology; oncoproteins; protein structure function; viral carcinogenesis; virus related neoplasm /cancer

DESCRIPTION: (Applicant's Description) Kaposi's sarcoma (KS) is the leading neoplasm of AIDS patients, and HIV infection is a strong risk factor for KS development. However, epidemiologic data indicate that HIV is not the sole determinant of KS risk and point to a sexually transmitted factor as being important in KS pathogenesis. Recently, the genome of a novel herpesvirus called KS-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) has been closely linked to KS tumors; this virus has been suggested as a candidate for the proposed cofactor. A complete understanding of the potential contribution(s) of KSHV/HHS8 to KS tumorigenesis will require a detailed knowledge of the viral genes expressed in the tumor. The applicant has cloned the entire genome of KSHV/HHV8, developed a cell culture system for virus production, and identified two abundant viral transcripts expressed in KS tumor cells. These RNAs are highly distinctive and are not closely analogous to known gene products of related gamma herpesviruses. This project will further characterize these viral genes and identify and characterize additional viral genes expressed in KS. The protein products of these genes will be characterized biochemically and functionally, with particular attention to their potential to influence cellular growth control and differentiation. These studies should provide new molecular clues to the potential roles of KSHV/HHV8 in KS and could identify new targets for therapeutic intervention in the future.

描述：（申请人的描述） Kaposi的肉瘤（KS）是艾滋病患者的领先肿瘤，HIV 感染是KS开发的强大风险因素。 然而， 流行病学数据表明，艾滋病毒不是KS风险的唯一决定因素 并指出一个在KS中很重要的性传播因素 发病。 最近，一个新型疱疹病毒的基因组称为 KS相关的疱疹病毒（KSHV）或人类疱疹病毒8（HHV8）已 与KS肿瘤密切相关；该病毒已被建议作为候选人 对于拟议的辅助因子。 对潜力的完全理解 KSHV/HHS8对KS肿瘤发生的贡献将需要详细 对肿瘤中表达的病毒基因的了解。 申请人有 克隆了KSHV/HHV8的整个基因组，开发了一种用于的细胞培养系统 病毒生产，并确定了两个在 KS肿瘤细胞。 这些RNA高度独特，不密切 类似于相关γ疱疹病毒的已知基因产物。 这 项目将进一步描述这些病毒基因并识别和 表征在Ks中表达的其他病毒基因。 蛋白质产品 这些基因将在生化和功能上以 特别注意其影响细胞生长控制的潜力 和分化。 这些研究应提供新的分子线索 KSHV/HHV8在KS中的潜在作用，可以确定 将来的治疗干预。