Structure and Molecular Composition of KSHV an RRV

KSHV 和 RRV 的结构和分子组成

• 批准号: 7882733
• 负责人: Dean H Kedes
• 金额: $ 5.29万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7882733
• 关键词: Acquired Immunodeficiency Syndrome; Antiviral Response; Architecture; B-Cell Neoplasm; Biochemical; Biology; Capsid; Cell Count; Cell Nucleus; Cells; Characteristics; Cryoelectron Microscopy; Data; Disease; Electrons; Environment; Future; Gene Proteins; Herpesviridae; Homologous Gene; Human Herpesvirus 8; Human Virus; Hyperplasia; Image; Imaging Techniques; Immunologics; Immunosuppression; Individual; Infection; Investigation; Kinetics; Knowledge; Lead; Lymphoma; Lymphoproliferative Disorders; Lytic; Macaca mulatta; Maps; Methods; Molecular; Molecular Structure; Names; Open Reading Frames; Persons; Play; Primates; Production; Proteins; Publishing; Research; Resolution; Rhadinovirus; Role; Shapes; Staging; Structural Protein; Structure; Testing; Therapeutic Intervention; Viral; Viral Genome; Viral Proteins; Virion; Virus; Virus Replication; Work; base; defined contribution; design; effusion; gammaherpesvirus; human disease; interest; knock-down; latent infection; lytic replication; meetings; molecular imaging; particle; reconstruction; research study; stoichiometry; tumor

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.

十年的流行病学和生物学研究已确定卡波西肉瘤 (KS) 相关疱疹病毒 (KSHV) 是同名肿瘤的感染原因。感染 这种伽马疱疹病毒还可以导致另外两种人类疾病，多中心卡斯尔门氏病， 淋巴组织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） 患有获得性免疫缺陷综合症（艾滋病）。尽管最初的 KSHV 暴露通常是 无症状，可能导致宿主体内有限数量的细胞潜伏感染， 免疫抑制可能导致不受控制的病毒传播、潜伏感染细胞的扩增，并最终导致病毒传播。 肿瘤形成。这种致病进展以及人与人之间的传播取决于裂解 病毒的重新激活和复制，然后是病毒的募集、感染和增生性扩张 新靶细胞的临界质量。裂解开始后出现的最显着的结构 复制是充满细胞核的二十面体衣壳，当完全成熟时，包含线性病毒 基因组。 我们在最初资助期间由 NIH 赞助的 KSHV 工作是第一个探索 同时分析衣壳的蛋白质组成、化学计量和三维结构 伽马疱疹病毒。我们在此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，恒河猴鼻病毒（RRV）。由于病毒颗粒必须含有宿主必需的蛋白质 范围确定和感染起始，全面鉴定其蛋白至关重要 作品。此外，了解这种成分是功能研究的先决条件。我们将 整合分子和成像技术来识别病毒颗粒相关蛋白和基因 对它们进行编码，同时表征病毒结构的更精细的细节。 我们提出的关于病毒结构、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目标。