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: 8846480
• 负责人: Eric M Wohlford
• 金额: --
• 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 2015-05-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8846480
• 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; Health; Herpesviridae; Human Herpesvirus 4; In Vitro; Individual; Infection; Kenya; Laboratories; Lead; Link; 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

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）：流行的伯基特淋巴瘤（EBL）是撒哈拉以南非洲最常见的儿科癌症。地方性BL是一种具有侵略性的B细胞淋巴瘤，具有两个感染性辅助因子：早期的爱泼斯坦Barr病毒（EBV）感染和恶性疟疾疟原虫疟疾。最近的研究表明，恶性疟原虫寄生虫增加了B细胞系的EBV裂解激活。结果表明，恶性疟原虫的寄生虫通过多克隆活化B细胞发挥其作用。恶性疟原虫寄生虫包含多个多克隆B细胞活化剂，包括CpG DNA，刺激了Toll样受体9（TLR9）。最近显示，使用CPG寡核苷酸序列激活B细胞会增加感染和EBV诱导的B细胞增殖。然而，尚未显示恶性疟原虫寄生虫是否增加了原发性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。通过定量PCR，我们观察到高疟疾区域的EBV感染细胞的频率增加了，与附近肯尼亚西部的低疟疾区域相比。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潜伏期的建立的影响。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载荷或改变EBV感染的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一项急性恶性疟疾疟疾研究来将我们的工作转化为诊所，以确定恶性疟原虫疟疾是否激活B细胞并增加其对体内EBV感染的敏感性。我们将比较来自恶性疟原虫疟疾患者和健康对照组的单个B细胞的B细胞激活和EBV感染。这将使我们能够得出关于哪种B细胞类型的结论，即我们在初步研究中观察到的EBV增加。总体而言，这项工作将决定恶性疟原虫和EBV的相互作用，目的是发现EBL的预防策略。