LSUHSC COBRE: DEFINING BONE MARROW AS A RESERVOIR FOR GAMMAHERPESVIRUS LATENCY

LSUHSC COBRE：将骨髓定义为伽玛疱疹病毒潜伏期的储库

• 批准号: 8359692
• 负责人: Scott A. Tibbetts
• 金额: $ 6.12万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359692
• 关键词: Animal Model; B-Lymphocytes; Bone Marrow; Carcinoma; Cells; Centers of Research Excellence; Chronic; Dendritic Cells; Development; Disease; Funding; Goals; Grant; Hematopoietic; Hematopoietic Stem Cell Transplantation; Human; Human Herpesvirus 4; Human Herpesvirus 8; Immune; Immunity; Infection; Latent Virus; Life; Lymphoma; Lymphoproliferative Disorders; Malignant Neoplasms; Molecular; Mus; National Center for Research Resources; Peripheral; Principal Investigator; Research; Research Infrastructure; Resources; Role; Source; Tissues; United States National Institutes of Health; Viral; Virus; Work; cell type; cost; design; gammaherpesvirus; in vivo; latent infection; macrophage; prevent; sarcoma; tumor; virology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Subproject #4: Gammaherpesvirus Latency and Immunity Scott A. Tibbetts The gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are associated with numerous malignancies in humans including lymphomas, carcinomas, and sarcomas, and are critical determinants of lymphoproliferative disease following hematopoietic stem cell transplantation. Gammaherpesviruses maintain life-long latent infection in restricted subsets of hematopoietic cells. Thus, defining cellular reservoirs that harbor latent virus and mechanisms that govern long-term infection is critical for designing rational strategies to prevent disease. In vivo studies of gammaherpesviruses in humans have been limited by the difficulties of working in the natural host. Murine gammaherpesvirus 68 (gHV68) is genetically related to EBV and KSHV and causes lymphoma and lymphoproliferative disease in mice, providing a small animal model for mechanistic in vivo studies of the virus/host relationship. Like EBV and KSHV, gHV68 latently infects peripheral B cells and other hematopoietic cells including tissue macrophages and dendritic cells. It is not understood how gammaherpesvirues gain access to these cells or how they establish latent infection. We hypothesize that the bone marrow is a reservoir for gammaherpesvirus latency and that infection of hematopoietic cells in the bone marrow facilitates chronic infection and disease. We will (i) define whether the bone marrow is a reservoir for latency, (ii) define the cell types infected in the bone marrow, and (iii) determine the role of bone marrow latency in viral dissemination and immune evasion. The long-term goal is to understand how gammaherpesviruses establish life-long latency in host immune cells and how alterations in that relationship result in the development of disease.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 子项目#4：伽马疱疹病毒潜伏期和免疫 斯科特·蒂贝茨 伽马疱疹病毒 Epstein-Barr 病毒 (EBV) 和卡波西肉瘤相关疱疹病毒 (KSHV) 与人类多种恶性肿瘤相关，包括淋巴瘤、癌和肉瘤，并且是造血干细胞移植后淋巴增殖性疾病的关键决定因素。 伽玛疱疹病毒在有限的造血细胞亚群中维持终生潜伏感染。 因此，确定隐藏潜伏病毒的细胞库和控制长期感染的机制对于设计预防疾病的合理策略至关重要。 人类伽马疱疹病毒的体内研究由于在自然宿主中工作的困难而受到限制。 鼠伽马疱疹病毒 68 (gHV68) 与 EBV 和 KSHV 有遗传相关性，可引起小鼠淋巴瘤和淋巴增殖性疾病，为病毒/宿主关系的体内机制研究提供小动物模型。 与 EBV 和 KSHV 一样，gHV68 潜伏感染外周 B 细胞和其他造血细胞，包括组织巨噬细胞和树突状细胞。 目前尚不清楚伽马疱疹病毒如何进入这些细胞或如何建立潜伏感染。 我们假设骨髓是伽玛疱疹病毒潜伏期的储存库，并且骨髓中造血细胞的感染促进了慢性感染和疾病。 我们将（i）定义骨髓是否是潜伏期的储存库，（ii）定义骨髓中感染的细胞类型，以及（iii）确定骨髓潜伏期在病毒传播和免疫逃避中的作用。 长期目标是了解伽玛疱疹病毒如何在宿主免疫细胞中建立终生潜伏期，以及这种关系的改变如何导致疾病的发展。