The interaction of Burkitt???s lymphoma cofactors EBV and Plasmodium

伯基特淋巴瘤辅助因子 EBV 和疟原虫的相互作用

• 批准号: 8574478
• 负责人: Eric M Wohlford
• 金额: $ 4.61万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-03 至 2016-05-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8574478
• 关键词: Acute; Affect; Africa South of the Sahara; African Burkitt' s lymphoma; Area; B Cell Proliferation; B-Cell Activation; B-Cell Lymphomas; B-Lymphocytes; Blood Flow Cytometry; Burkitt Lymphoma; Cell Line; Cells; Child; Clinic; Clinical; Complement 3d Receptors; DNA; Data; Development; District Hospitals; Epstein-Barr Virus Infections; Epstein-Barr Virus latency; Erythrocytes; Event; Exposure to; Falciparum Malaria; Frequencies; Goals; Herpesviridae; Human Herpesvirus 4; In Vitro; Individual; Infection; Kenya; Laboratories; Lead; Link; Lymphoma; Lytic; Lytic Phase; Malaria; Malignant Childhood Neoplasm; Malignant Neoplasms; Measures; Memory B-Lymphocyte; Modeling; Oligonucleotides; Parasites; Patients; Phenotype; Plasmodium; Plasmodium falciparum; Predisposition; Prevention therapy; Research; Research Infrastructure; Sampling; Source; TLR9 gene; Techniques; Testing; Tonsil; Translating; Viral Load result; Viral load measurement; Virus; Work; antimicrobial; base; cell type; cofactor; density; design; field study; in vivo; infected B cell; peripheral blood; polyclonal B cell activator; prevent; public health relevance

DESCRIPTION (provided by applicant): Endemic Burkitt's lymphoma (eBL) is the most common pediatric cancer in sub-Saharan Africa. Endemic BL is an aggressive B cell lymphoma with two infectious cofactors: early Epstein Barr virus (EBV) infection and frequent Plasmodium falciparum malaria. Recent research suggests that P. falciparum parasites increase the lytic activation of EBV from B cell lines. It was shown that P. falciparum parasites exert their effect o EBV through polyclonal activation B cells. Plasmodium falciparum parasites contain multiple polyclonal B cell activators, including CpG DNA, which stimulates toll-like receptor 9 (TLR9). It was recently shown that activation of B cells using CpG oligonucleotide sequences increased the infection and EBV-induced proliferation of B cells. It has not been shown, however, whether P. falciparum parasites increase the primary EBV infection and EBV-induced proliferation of B cells. Our preliminary in vitro and in vivo studies suggest that P. falciparum indeed increases these measures. We observed an increased frequency of EBV infected cells in children in a high malaria area compared to those in a nearby low malaria area of western Kenya by quantitative PCR. To further determine the interaction of P. falciparum and EBV in regard to eBL we have proposed the following studies. We will complete an in vitro study to determine the effects of P. falciparum on the establishment of EBV latency. We hypothesize that exposure to P. falciparum parasites will increase the EBV-induced proliferation, EBV load, or alter the EBV infected B cell phenotype of B cells in vitro. We will also translate our work to the clinic by performing an acute P. falciparum malaria field study in western Kenya to determine whether P. falciparum malaria activates B cells and increases their susceptibility to EBV infection in vivo. We will compare the B cell activation and EBV infection of individual B cells from P. falciparum malaria patients and healthy controls. This will allow us to make conclusions about which B cell type harbors the increased EBV we observed with our preliminary studies. Overall, this work will determine the interaction of P. falciparum and EBV with the goal of discovering preventative strategies for eBL.

描述（由申请人提供）：地方性伯基特淋巴瘤（eBL）是撒哈拉以南非洲地区最常见的儿科癌症。地方性 BL 是一种侵袭性 B 细胞淋巴瘤，具有两种传染性辅因子：早期 Epstein Barr 病毒 (EBV) 感染和频繁的恶性疟原虫疟疾。最近的研究表明，恶性疟原虫寄生虫增加了 B 细胞系 EBV 的裂解激活。结果表明，恶性疟原虫通过多克隆激活 B 细胞对 EBV 发挥作用。恶性疟原虫寄生虫含有多种多克隆 B 细胞激活剂，包括可刺激 Toll 样受体 9 (TLR9​​) 的 CpG DNA。最近表明，使用 CpG 寡核苷酸序列激活 B 细胞会增加 B 细胞的感染和 EBV 诱导的增殖。然而，尚未证明恶性疟原虫寄生虫是否会增加原发性 EBV 感染和 EBV 诱导的 B 细胞增殖。我们的初步体外和体内研究表明，恶性疟原虫确实增加了这些措施。我们通过定量 PCR 观察到，与肯尼亚西部疟疾低发区附近的儿童相比，疟疾高发区儿童中 EBV 感染细胞的频率有所增加。为了进一步确定恶性疟原虫和 EBV 在 eBL 方面的相互作用，我们提出了以下研究。我们将完成一项体外研究，以确定恶性疟原虫对 EBV 潜伏期建立的影响。我们假设，暴露于恶性疟原虫寄生虫会增加 EBV 诱导的增殖、EBV 负载，或改变体外 B 细胞的 EBV 感染 B 细胞表型。我们还将通过在肯尼亚西部进行急性恶性疟原虫疟疾现场研究将我们的工作转化为临床，以确定恶性疟原虫疟疾是否会激活 B 细胞并增加其体内对 EBV 感染的易感性。我们将比较恶性疟疾患者和健康对照个体 B 细胞的 B 细胞活化和 EBV 感染。这将使我们能够得出关于哪种 B 细胞类型携带我们在初步研究中观察到的 EBV 增加的结论。总体而言，这项工作将确定恶性疟原虫和 EBV 的相互作用，目的是发现 eBL 的预防策略。