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

描述(申请人提供)：地方性Burkitt淋巴瘤(EBL)是撒哈拉以南非洲最常见的儿童癌症。地方性淋巴瘤是一种侵袭性B细胞淋巴瘤，有两个感染辅助因素：早期EB病毒感染和频繁的恶性疟疾。最近的研究表明，恶性疟原虫能增加B细胞系EBV的裂解活性。结果表明，恶性疟原虫通过多克隆激活B细胞发挥抗EBV作用。恶性疟原虫含有多种多克隆B细胞激活剂，包括刺激Toll样受体9(TLR9)的CpG DNA。最近的研究表明，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，恶性疟原虫是否会增加原发EBV感染和EBV诱导的B细胞增殖仍未见报道。我们在体外和体内的初步研究表明，恶性疟原虫确实增加了这些措施。我们通过定量聚合酶链式反应观察到，与附近肯尼亚西部疟疾低发区的儿童相比，疟疾高发区儿童中EBV感染细胞的频率增加。为了进一步确定恶性疟原虫和EB病毒在EBL中的相互作用，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建立EBV潜伏期的影响。我们推测，暴露于恶性疟原虫会增加EB病毒诱导的B细胞的增殖、EBV载量，或在体外改变EBV感染的B细胞表型。我们还将把我们的工作转移到临床上，在肯尼亚西部进行一项恶性疟疾急性现场研究，以确定恶性疟疾是否激活了B细胞，并增加了它们在体内对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细胞的激活和EBV感染情况。这将使我们能够得出结论，哪些B细胞类型含有我们在初步研究中观察到的EBV增加。总体而言，这项工作将确定恶性疟原虫和EBV的相互作用，目标是发现EBL的预防策略。

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.