HERPESVIRAL GENE EXPRESSION IN KAPOSIS SARCOMA

描述：(申请人描述) 卡波西肉瘤(KS)是艾滋病患者的主要肿瘤，而HIV 感染是KS发生的强烈危险因素。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 并指出性传播因素在KS中很重要 发病机制。最近，一种新的疱疹病毒的基因组 KS相关疱疹病毒(KSHV)或人类疱疹病毒8型(HHV8)已被 与KS肿瘤密切相关；这种病毒已被建议为候选病毒 对于提议的余因数。对潜力的全面理解 KSHV/HHS8对KS肿瘤发生的贡献(S)需要详细的 了解肿瘤中表达的病毒基因。申请人有 克隆了KSHV/HHV8的全基因组，建立了一套细胞培养体系 病毒的产生，并鉴定了两个丰富的病毒转录本，在 KS肿瘤细胞。这些RNA具有很高的区别性，并且不是很接近 与已知的相关伽马疱疹病毒的基因产物相似。这 该项目将进一步表征这些病毒基因，并识别和 鉴定在KS中表达的其他病毒基因。蛋白质产品 在这些基因中，将有生化和功能方面的特征， 特别注意它们影响细胞生长控制的潜力 和差异化。这些研究应该会提供新的分子线索 KSHV/HHV8在KS中的潜在作用并可能识别新的靶点 未来的治疗性干预。

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.