Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, Ohio, USA.
J Infect Dis. 2024 Jan 12;229(1):73-82. doi: 10.1093/infdis/jiad264.
The 2 cofactors in the etiology of Burkitt lymphoma (BL) are Epstein-Barr virus (EBV) and repeated Plasmodium falciparum malaria infections. This study evaluated EBV loads in mucosal and systemic compartments of children with malaria and controls. Age was analyzed as a covariate because immunity to malaria in endemic regions is age dependent.
Children (2-10 years) with clinical malaria from Western Kenya and community controls without malaria were enrolled. Saliva and blood samples were collected, EBV viral load was assessed by quantitative polymerase chain reaction, and EpiTYPER MassARRAY was used to assess methylation of 3 different EBV genes.
Regardless of the compartment, we detected EBV more frequently in malaria cases compared to controls, although the difference was not significant. When EBV was detected, there were no differences in viral load between cases and controls. However, EBV methylation was significantly lower in the malaria group compared to controls in both plasma and saliva (P < .05), indicating increased EBV lytic replication. In younger children before development of immunity to malaria, there was a significant effect of malaria on EBV load in peripheral blood mononuclear cells (P = .04).
These data suggest that malaria can directly modulate EBV persistence in children, increasing their risk for BL.
伯基特淋巴瘤(BL)的两个病因因素是 Epstein-Barr 病毒(EBV)和反复感染疟原虫。本研究评估了疟疾患儿和对照儿的黏膜和全身部位 EBV 载量。年龄作为协变量进行分析,因为在流行地区,对疟疾的免疫力取决于年龄。
从肯尼亚西部招募了患有临床疟疾的儿童(2-10 岁)和没有疟疾的社区对照儿。采集唾液和血液样本,通过定量聚合酶链反应评估 EBV 病毒载量,并使用 EpiTYPER MassARRAY 评估 3 种不同 EBV 基因的甲基化。
无论在哪个部位,我们都发现疟疾病例中 EBV 的检出频率高于对照组,尽管差异无统计学意义。当 EBV 被检出时,病例组和对照组之间的病毒载量没有差异。然而,与对照组相比,疟疾组血浆和唾液中的 EBV 甲基化水平显著降低(P <.05),表明 EBV 裂解复制增加。在尚未产生抗疟疾免疫力的年幼儿童中,疟疾对外周血单核细胞中的 EBV 载量有显著影响(P =.04)。
这些数据表明,疟疾可以直接调节儿童体内 EBV 的持续存在,增加其患 BL 的风险。