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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 子项目4：伽马疱疹病毒潜伏期和免疫力 斯科特·A·蒂贝茨 伽玛疱疹病毒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有关，包括淋巴瘤、癌和肉瘤，是造血干细胞移植后淋巴增生性疾病的关键决定因素。伽马疱疹病毒在有限的造血细胞亚群中维持终身潜伏感染。因此，确定蕴藏潜伏病毒的细胞储备库和管理长期感染的机制对于设计合理的预防疾病策略至关重要。由于在自然宿主中工作的困难，在人体内对伽马疱疹病毒的体内研究一直受到限制。小鼠伽马疱疹病毒68(GHV68)与EBV和KSHV有遗传关系，可引起小鼠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一个小动物模型。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。目前还不清楚伽马疱疹病毒是如何进入这些细胞的，也不知道它们是如何建立潜伏感染的。我们假设骨髓是伽马疱疹病毒潜伏期的储存库，骨髓中造血细胞的感染促进了慢性感染和疾病的发生。我们将(I)确定骨髓是否是潜伏期的储存库，(Ii)定义在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身潜伏期，以及这种关系的变化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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.