Structure and Molecular Composition of KSHV an RRV

十年的流行病学和生物学研究已经牢固地确立了卡波西肉瘤 (KS)相关疱疹病毒(KSHV)是与其同名的肿瘤的感染性原因。感染 这种伽马疱疹病毒还可以导致另外两种人类疾病，多中心性卡斯特尔曼病， 淋巴增生性疾病和原发性渗出性淋巴瘤，这是一种最常困扰患者的B细胞肿瘤 患有获得性免疫缺陷综合征(艾滋病)。尽管最初的KSHV暴露通常是 无症状，并可能导致宿主中有限数量的细胞潜伏感染， 免疫抑制可导致病毒不受控制的传播，潜伏感染细胞的扩张，并最终 肿瘤的形成。这种致病进展以及人与人之间的传播依赖于溶血素 病毒的重新激活和复制，以及随后的招募、感染和增生性扩张 新靶细胞的临界质量。在溶血开始后出现的最显著的结构 复制是充满细胞核的二十面体衣壳，当完全成熟时，携带线状病毒。 基因组。 我们在初始资助期间由美国国立卫生研究院赞助的KSHV工作是第一次探索 同时测定了沙门氏菌衣壳的蛋白质组成、化学计量和三维结构。 伽马疱疹病毒。我们在这份申请中建议将这些研究扩展到一个全面的 了解病毒粒子的组成和结构，检查KSHV及其有用的灵长类动物 同源物，恒河猴轮状病毒(RRV)。因为病毒粒子必须含有宿主必需的蛋白质 范围的确定和感染的开始，关键是要全面鉴定它们的蛋白质 组成。此外，对这种成分的了解是进行功能研究的先决条件。我们的遗嘱 结合分子和成像技术识别病毒粒子相关蛋白和基因 对它们进行编码，同时描述病毒体系结构的更精细细节。 我们对病毒结构、分子组成和组装的研究结果可能会有所帮助。 确定未来治疗干预的新靶点。

A decade of both epidemiologic and biologic research has firmly established Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) as the infectious cause of the tumor that shares its name. Infection with this gammaherpesvirus can also lead to two other human diseases, multicentric Castlemen's disease, a lymphoproliferative disorder, and primary effusion lymphoma, a B cell tumor most often afflicting persons with acquired immune deficiency syndrome (AIDS). Although initial KSHV exposure is generally asymptomatic and likely results in the latent infection of a limited number of cells in the host, immunosuppression can lead to unchecked viral spread, expansion of latently infected cells and eventual tumor formation. This pathogenic progression as well as person-to-person spread depends on lytic reactivation and replication of virus followed by recruitment, infection and hyperplastic expansion of a critical mass of new target cells. The most remarkable structures to appear following the initiation of lytic replication are the icosahedral capsids that fill the nucleus and, when fully mature, harbor the linear viral genome. Our NIH-sponsored work on KSHV during the initialfunding period was the first to explore simultaneously the protein composition, stoichiometry andthree-dimensional structure of capsids from a gammaherpesvirus. We propose in this application to extend these studies toward a comprehensive understanding of the composition and structure of the virions, examining both KSHV and its useful primate homolog, Rhesus monkey rhadinovirus (RRV). Since virions must contain the proteins essential for host range determination and initiation of infection, it is critical to comprehensively identify their protein composition. Moreover, knowledge of this composition is a prerequisite for functional investigations. Wewill integrate molecular and imaging techniques to identify the virion-associated proteins and the genes encoding them while characterizing the finer details of the viral architecture. The results of our proposed studies on viral structure, molecular composition and assembly may help identify new targets for therapeutic intervention in the future.