The mycotoxin aflatoxin B1 stimulates Epstein-Barr virus-induced B-cell transformation in in vitro and in vivo experimental models
The mycotoxin aflatoxin B1 stimulates Epstein-Barr virus-induced B-cell transformation in in vitro and in vivo experimental models
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DOI：
10.1093/carcin/bgv142
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发表时间：
2015-11-01
期刊：
影响因子：
4.7
通讯作者：
Tommasino, Massimo
中科院分区：
文献类型：
--
作者：
Accardi, Rosita;Gruffat, Henri;Tommasino, Massimo
尽管eb病毒（EBV）感染广泛分布，但某些EBV驱动的恶性肿瘤在地理上受到限制。ebv相关的伯基特淋巴瘤（eBL）在撒哈拉以南非洲儿童中流行。这一人群严重暴露于受霉菌毒素黄曲霉毒素B1 （AFB1）污染的食物。在这里，我们表明，在体外和体内模型中暴露于AFB1可诱导EBV裂解周期的激活并增加EBV负荷，这两个事件与体内eBL风险增加有关。AFB1处理导致细胞基因表达的改变，随后激活信号通路，如PI3K，进而介导EBV生命周期的再激活。最后，我们发现AFB1在原代人B细胞和人源化动物模型中都能触发ebv驱动的细胞转化。总之，我们的数据为AFB1在ebv介导的癌变中作为辅助因子的作用提供了证据。
Although Epstein-Barr virus (EBV) infection is widely distributed, certain EBV-driven malignancies are geographically restricted. EBV-associated Burkitt's lymphoma (eBL) is endemic in children living in sub-Saharan Africa. This population is heavily exposed to food contaminated with the mycotoxin aflatoxin B1 (AFB1). Here, we show that exposure to AFB1 in in vitro and in vivo models induces activation of the EBV lytic cycle and increases EBV load, two events that are associated with an increased risk of eBL in vivo. AFB1 treatment leads to the alteration of cellular gene expression, with consequent activations of signaling pathways, e.g. PI3K, that in turn mediate reactivation of the EBV life cycle. Finally, we show that AFB1 triggers EBV-driven cellular transformation both in primary human B cells and in a humanized animal model. In summary, our data provide evidence for a role of AFB1 as a cofactor in EBV-mediated carcinogenesis.