Structure and Molecular Composition of KSHV an RRV

十年的流行病学和生物学研究已经确定卡波西肉瘤 （KS）相关疱疹病毒（KSHV）作为肿瘤的感染原因，与其同名。感染 这种γ疱疹病毒也会导致另外两种人类疾病，多中心Castlemen病， 淋巴增生性疾病和原发性渗出性淋巴瘤，一种最常折磨人的B细胞肿瘤 获得性免疫缺陷综合症（艾滋病）虽然最初的KSHV接触通常是 无症状并且可能导致宿主中有限数量细胞的潜伏感染， 免疫抑制可导致病毒不受抑制地扩散，潜伏感染细胞的扩增， 肿瘤形成这种致病性进展以及人与人之间的传播取决于溶解性 病毒的重新激活和复制，然后招募，感染和增生性扩张， 新靶细胞的临界质量。最显著的结构出现后，开始溶解 复制是二十面体的衣壳，填充细胞核，当完全成熟时， 基因组 在最初的资助期间，我们的NIH赞助的关于KSHV的工作是第一个探索 同时，从一个衣壳的蛋白质组成，化学计量和三维结构， γ疱疹病毒我们在本申请中建议将这些研究扩展到全面的 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，恒河猴鼻状病毒（RRV）。由于病毒体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 混合物.此外，这种组合物的知识是功能研究的先决条件。威威尔 整合分子和成像技术以鉴定病毒体相关蛋白和基因 编码它们，同时表征病毒结构的更精细的细节。 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.