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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 子项目#4：γ疱疹病毒潜伏期和免疫力 Scott A. Tibbetts γ疱疹病毒Epstein-Barr病毒（EBV）和卡波西肉瘤相关疱疹病毒（KSHV）与人类的许多恶性肿瘤（包括淋巴瘤、癌和肉瘤）相关，并且是造血干细胞移植后淋巴增生性疾病的关键决定因素。 γ疱疹病毒在造血细胞的有限亚群中维持终身潜伏感染。 因此，确定潜伏病毒的细胞库和控制长期感染的机制对于设计合理的预防疾病的策略至关重要。 人体γ疱疹病毒的体内研究受到在自然宿主中工作困难的限制。 鼠γ疱疹病毒68（gHV 68）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/宿主关系的体内机制研究提供了小动物模型。 与EBV和KSHV一样，gHV 68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细胞。 目前尚不清楚γ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γ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慢性感染和疾病。 我们将（i）确定骨髓是否是潜伏期的储存库，（ii）确定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。 长期目标是了解γ疱疹病毒如何在宿主免疫细胞中建立终身潜伏期，以及这种关系的改变如何导致疾病的发展。

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.