Infection of primary B cells by the human lymphomagenic pathogen HHV8
人类淋巴瘤病原体 HHV8 感染原代 B 细胞
基本信息
- 批准号:7614767
- 负责人:
- 金额:$ 2.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-03-01 至 2014-02-28
- 项目状态:已结题
- 来源:
- 关键词:B Cell ProliferationB-Cell ActivationB-Lymphocyte SubsetsB-LymphocytesBiologyCandidate Disease GeneCell SurvivalCellsDNADiseaseEnsureEnvironmentGoalsHumanHuman Herpesvirus 4Human Herpesvirus 8Human VirusImaging technologyImmune System DiseasesImmunocompromised HostIn VitroIndividualInfectionInvestigationKaposi SarcomaLaboratoriesLeadLifeLymphomaMalignant - descriptorMalignant NeoplasmsMemoryMorbidity - disease rateMulticentric Angiofollicular Lymphoid HyperplasiaMultimodal ImagingOncogenicPathogenesisPathway interactionsPatientsPhenotypePreventionProcessReverse Transcriptase Polymerase Chain ReactionSignal PathwaySignal TransductionViral GenesViral GenomeViral ProteinsVirusWestern Blottingbiomedical scientistcancer typecell motilitycell transformationeffusiongammaherpesvirusin vivoinfected B cellinsightmetaplastic cell transformationmortalitypathogenprotein expressionpublic health relevanceresidencetherapeutic targettooltumorigenic
项目摘要
DESCRIPTION (provided by applicant): Primary effusion lymphoma (PEL) and multicentric Castleman's disease arise in immunocompromised patients harboring human herpesvirus 8 (HHV8), the same oncogenic pathogen underlying Kaposi's sarcoma. Like EBV, HHV8 establishes lifelong infection by latently infecting B cells and expresses viral proteins capable of modulating B cell signaling and survival. Yet, in stark contrast to EBV, KSHV-infected cells are extremely rare in asymptomatic individuals, and efficient in vitro infection of B cells with KSHV has proven difficult. This suggests that KSHV may infect a small subset of B cells. The long-term goals of this project are to understand the biology and pathogenesis underlying primary B cell infection, examining the hypothesis that the target B cells may represent a unique environment allowing, in the setting of immunocompromise, cellular transformation. We hope to better understand the rules governing this process, with our initial goals being to: 1. Identify the subset(s) of B cells that support KSHV infection. We will utilize high throughput multimodal imaging technology to identify B cell targets of KSHV infection. Appreciating that infection may alter the B cell phenotype, we will confirm the identity of KSHV targets by isolating B cell subsets prior to infection and comparing the efficiency of infection in each subset. 2. Determine the effects of KSHV infection on B cell survival and function and identify candidate genes responsible for these changes. We will focus initial studies on KSHV-induced changes by examining proliferative capacity, survival and transformation ability in vitro. In parallel to these functional studies, we will use mini-microarrays focused on B cell activation pathways, followed by quantitative RT-PCR and/or western blot, to identify changes in cell signaling pathways that may be responsible for potential phenotypic changes. PUBLIC HEALTH RELEVANCE: Cancers and diseases of the immune cells in patients lead to significant morbidity and mortality throughout the world. Unfortunately, the rules governing how these diseases arise and how a healthy cell transforms into a malignant one remain unclear. By examining in the laboratory human viruses that can cause these types of cancers, it is our hope that we will gain insights into these rules, providing biomedical scientist the tools with which to develop better therapies and preventions.
描述(由申请人提供):原发性渗出性淋巴瘤(PEL)和多中心卡斯尔曼氏病发生在携带人类疱疹病毒 8(HHV8)的免疫功能低下的患者中,该病毒与卡波西肉瘤的致癌病原体相同。与 EBV 一样,HHV8 通过潜伏感染 B 细胞建立终生感染,并表达能够调节 B 细胞信号传导和存活的病毒蛋白。然而,与 EBV 形成鲜明对比的是,KSHV 感染的细胞在无症状个体中极为罕见,并且 KSHV 在体外有效感染 B 细胞已被证明是困难的。这表明 KSHV 可能感染一小部分 B 细胞。该项目的长期目标是了解原发性 B 细胞感染的生物学和发病机制,检验靶 B 细胞可能代表一个独特的环境,在免疫功能低下的情况下允许细胞转化的假设。我们希望更好地理解控制这一过程的规则,我们的初步目标是: 1. 识别支持 KSHV 感染的 B 细胞子集。我们将利用高通量多模态成像技术来识别 KSHV 感染的 B 细胞靶点。认识到感染可能会改变 B 细胞表型,我们将通过在感染前分离 B 细胞亚群并比较每个亚群的感染效率来确认 KSHV 靶点的身份。 2. 确定 KSHV 感染对 B 细胞存活和功能的影响,并确定导致这些变化的候选基因。我们将通过检查体外增殖能力、存活和转化能力来重点研究 KSHV 引起的变化。在进行这些功能研究的同时,我们将使用专注于 B 细胞激活途径的微型微阵列,然后进行定量 RT-PCR 和/或蛋白质印迹,以确定可能导致潜在表型变化的细胞信号传导途径的变化。公共卫生相关性:癌症和患者免疫细胞疾病导致全世界显着的发病率和死亡率。不幸的是,这些疾病如何产生以及健康细胞如何转变为恶性细胞的规则仍不清楚。通过在实验室检查可导致这些类型癌症的人类病毒,我们希望能够深入了解这些规则,为生物医学科学家提供开发更好的治疗和预防的工具。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Lynn M Hassman其他文献
Lynn M Hassman的其他文献
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{{ truncateString('Lynn M Hassman', 18)}}的其他基金
Resolution of ocular inflammation: the role of type 1 conventional dendritic cells
解决眼部炎症:1 型常规树突状细胞的作用
- 批准号:
10449898 - 财政年份:2022
- 资助金额:
$ 2.76万 - 项目类别:
Resolution of ocular inflammation: the role of type 1 conventional dendritic cells
解决眼部炎症:1 型常规树突状细胞的作用
- 批准号:
10621794 - 财政年份:2022
- 资助金额:
$ 2.76万 - 项目类别:
Infection of primary B cells by the human lymphomagenic pathogen HHV8
人类淋巴瘤病原体 HHV8 感染原代 B 细胞
- 批准号:
8034767 - 财政年份:2009
- 资助金额:
$ 2.76万 - 项目类别:
Infection of primary B cells by the human lymphomagenic pathogen HHV8
人类淋巴瘤病原体 HHV8 感染原代 B 细胞
- 批准号:
8231302 - 财政年份:2009
- 资助金额:
$ 2.76万 - 项目类别:
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