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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 子标记＃4：伽马梅普斯病毒潜伏期和免疫力 Scott A. Tibbetts γ鞘菌病毒Epstein-Barr病毒（EBV）和Kaposi与肉瘤相关的疱疹病毒（KSHV）与人类中的许多恶性肿瘤有关，包括淋巴瘤，癌和肉瘤，并且是淋巴细胞学疾病的重要决定性的淋巴细胞症状。 伽马广播病毒维持造血细胞受限子集的终身潜在感染。 因此，定义具有潜在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理性策略至关重要。 人类γ鞘病毒的体内研究受到自然宿主工作困难的限制。 鼠伽马疱疹病毒68（GHV68）在遗传上与EBV和KSHV相关，并在小鼠中引起淋巴瘤和淋巴增生性疾病，为病毒/宿主关系的体内研究提供了小型动物模型。 像EBV和KSHV一样，GHV68潜在地感染外围B细胞和其他造血细胞，包括组织巨噬细胞和树突状细胞。 尚不清楚γ掌病毒如何访问这些细胞或它们如何建立潜在感染。 我们假设骨髓是γ鞘病毒潜伏期的储层，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层，（ii）定义骨髓中感染的细胞类型，（iii）确定骨髓潜伏期在病毒传播和免疫逃避中的作用。 长期的目标是了解γ掌病毒如何在宿主免疫细胞中建立终身潜伏期，以及该关系的改变如何导致疾病的发展。