The mycotoxin aflatoxin B1 stimulates Epstein-Barr virus-induced B-cell transformation in in vitro and in vivo experimental models.

Abstract:

: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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Accardi R,Gruffat H,Sirand C,Fusil F,Gheit T,Hernandez-Vargas H,Le Calvez-Kelm F,Traverse-Glehen A,Cosset FL,Manet E,Wild CP,Tommasino M

doi

10.1093/carcin/bgv142

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

1440-51

issue

11

eissn

0143-3334

issn

1460-2180

pii

bgv142

journal_volume

36

pub_type

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