Njie Ramou, Bell Andrew I, Jia Hui, Croom-Carter Debbie, Chaganti Sridhar, Hislop Andrew D, Whittle Hilton, Rickinson Alan B
Cancer Research UK Institute for Cancer Studies, The Medical School, University of Birmingham, Birmingham, United Kingdom.
J Infect Dis. 2009 Jan 1;199(1):31-8. doi: 10.1086/594373.
To investigate how intense Plasmodium falciparum infection predisposes to Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL), we analyzed the effect of acute malaria on existing EBV-host balance.
EBV genome loads in peripheral blood mononuclear cells were assayed by quantitative polymerase chain reaction, and EBV-specific CD8(+) T cell responses were assayed by interferon-gamma enzyme-linked immunospot assay.
Gambian children, from whom samples were obtained during an acute malaria attack and again up to 6 weeks later, had extremely high viral loads, reaching levels that in the United Kingdom are seen only in patients with infectious mononucleosis. Gambian control subjects (children and adults with no recent history of malaria) had lower median viral loads, although they were still >10-fold above the median for healthy UK adults. Limited experiments with EBV epitope peptides (restricted through the HLA-B 3501 and HLA-B 5301 alleles) also suggested an impairment of virus-specific CD8(+) T cell function in children with malaria, but only during acute disease.
Acute malaria is associated with sustained increase in EBV load and, possibly, a transient decrease in EBV-specific T cell surveillance. We infer that the unusually high set point of virus carriage in P. falciparum-challenged populations, allied with the parasite's capacity to act as a chronic B cell stimulus, probably contributes to the pathogenesis of endemic BL.
为了研究恶性疟原虫感染强度如何导致爱泼斯坦-巴尔病毒(EBV)阳性的伯基特淋巴瘤(BL),我们分析了急性疟疾对现有EBV-宿主平衡的影响。
通过定量聚合酶链反应检测外周血单个核细胞中的EBV基因组载量,通过干扰素-γ酶联免疫斑点试验检测EBV特异性CD8(+) T细胞反应。
在急性疟疾发作期间采集样本,6周后再次采集样本的冈比亚儿童,其病毒载量极高,达到在英国仅在传染性单核细胞增多症患者中才可见的水平。冈比亚对照受试者(近期无疟疾病史的儿童和成人)的病毒载量中位数较低,尽管仍比健康英国成年人的中位数高10倍以上。对EBV表位肽(通过HLA-B 3501和HLA-B 5301等位基因限制)进行的有限实验也表明,疟疾患儿的病毒特异性CD8(+) T细胞功能受损,但仅在急性疾病期间。
急性疟疾与EBV载量持续增加以及EBV特异性T细胞监测可能短暂下降有关。我们推断,在受到恶性疟原虫挑战的人群中,病毒携带的异常高设定点,加上寄生虫作为慢性B细胞刺激物的能力,可能有助于地方性BL的发病机制。