title: 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.
authors.affiliation: International Agency for Research on Cancer (IARC), World Health Organization, Lyon 69372, France, accardi@iarc.fr.
authors.forename: Rosita
authors.initials: R
authors.lastname: Accardi
authors.affiliation: EVIR and Oncogenic Herpesviruses Teams, International Center for Infectiology Research, Université de Lyon, Lyon 69007, France, INSERM, U1111, Lyon 69007, France, Human Virology, Ecole Normale Supérieure de Lyon, Lyon 69007, France, Centre International de Recherche en Infectiologie, Université Lyon 1, Lyon 69007, France and.
authors.forename: Henri
authors.initials: H
authors.lastname: Gruffat
authors.affiliation: International Agency for Research on Cancer (IARC), World Health Organization, Lyon 69372, France.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Sirand
authors.affiliation: EVIR and Oncogenic Herpesviruses Teams, International Center for Infectiology Research, Université de Lyon, Lyon 69007, France, INSERM, U1111, Lyon 69007, France, Human Virology, Ecole Normale Supérieure de Lyon, Lyon 69007, France, Centre International de Recherche en Infectiologie, Université Lyon 1, Lyon 69007, France and.
authors.forename: Floriane
authors.initials: F
authors.lastname: Fusil
authors.affiliation: International Agency for Research on Cancer (IARC), World Health Organization, Lyon 69372, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Gheit
authors.affiliation: International Agency for Research on Cancer (IARC), World Health Organization, Lyon 69372, France.
authors.forename: Hector
authors.initials: H
authors.lastname: Hernandez-Vargas
authors.affiliation: International Agency for Research on Cancer (IARC), World Health Organization, Lyon 69372, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Le Calvez-Kelm
authors.affiliation: Laboratoire d'anatomie et cytologie pathologiques, Centre Hospitalier Lyon-Sud, Lyon 69495, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Traverse-Glehen
authors.affiliation: EVIR and Oncogenic Herpesviruses Teams, International Center for Infectiology Research, Université de Lyon, Lyon 69007, France, INSERM, U1111, Lyon 69007, France, Human Virology, Ecole Normale Supérieure de Lyon, Lyon 69007, France, Centre International de Recherche en Infectiologie, Université Lyon 1, Lyon 69007, France and.
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
authors.affiliation: EVIR and Oncogenic Herpesviruses Teams, International Center for Infectiology Research, Université de Lyon, Lyon 69007, France, INSERM, U1111, Lyon 69007, France, Human Virology, Ecole Normale Supérieure de Lyon, Lyon 69007, France, Centre International de Recherche en Infectiologie, Université Lyon 1, Lyon 69007, France and.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Manet
authors.affiliation: International Agency for Research on Cancer (IARC), World Health Organization, Lyon 69372, France.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Wild
authors.affiliation: International Agency for Research on Cancer (IARC), World Health Organization, Lyon 69372, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tommasino
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology*; D002051:Burkitt Lymphoma / Q000139:chemically induced / Q000821:virology*; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002478:Cells, Cultured; D004781:Environmental Exposure; D020031:Epstein-Barr Virus Infections / Q000473:pathology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D015398:Signal Transduction; D014775:Virus Activation; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016604:Aflatoxin B1