HERPESVIRAL GENE EXPRESSION IN KAPOSIS SARCOMA

描述：（申请人的描述） 卡波西肉瘤（KS）是艾滋病患者的主要肿瘤， 感染是KS发展的一个强有力的危险因素。 但是，在这方面， 流行病学数据表明，HIV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）或人疱疹病毒8（HHV 8）已被 与KS肿瘤密切相关;该病毒已被建议作为候选病毒 对于所提议的辅因子。 完全了解潜在的 KSHV/HHS 8对KS肿瘤发生的贡献将需要详细的 了解肿瘤中表达的病毒基因。 申请人已经 克隆了KSHV/HHV 8的全基因组，建立了KSHV/HHV 8的细胞培养体系， 病毒的生产，并确定了两个丰富的病毒转录表达， KS肿瘤细胞。 这些RNA是高度独特的， 类似于相关γ疱疹病毒的已知基因产物。 这 该项目将进一步表征这些病毒基因，并识别和 表征KS中表达的其他病毒基因。 的蛋白质产物 这些基因的特点是生化和功能， 特别注意它们影响细胞生长控制的潜力 和差异化。 这些研究应该为以下方面提供新的分子线索： KSHV/HHV 8在KS中的潜在作用，并可以确定新的靶点， 未来的治疗干预。

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.