Aflatoxin B1 and Epstein Barr virus-induced CCL22 expression stimulates B cell infection

Scientists from the International Agency for Research on Cancer (IARC) and partner institutions have made an important discovery that may help to explain why endemic Burkitt lymphoma, a fast-growing cancer of the lymphatic system with a high mortality rate, develops much more commonly in children in some regions of Africa than anywhere else in the world. The study was published in the journal PNAS.

The researchers wanted to gain critical insights into how exposure to known cancer risk factors could drive the development of endemic Burkitt lymphoma. Epstein–Barr virus (EBV) – a common virus with which more than 90% of the adult human population worldwide is infected during their lives – is widely known to be associated with endemic Burkitt lymphoma. However, because infection with EBV is common but the development of endemic Burkitt lymphoma is relatively rare and its geographical distribution is unequal, other risk factors that are prevalent in the affected regions are also expected to play a role.

The scientists tested how exposure to EBV and exposure to mycotoxins – toxins produced by fungi commonly found in food in these regions – influenced how cells reacted and the proteins and other biomolecules that they produced. The researchers found that exposure of B cells to aflatoxin B1, a common mycotoxin in Africa, causes overexpression of a molecule called chemokine ligand 22 (CCL22), which plays a role in immunity. This overexpression of CCL22 increased the infection of B cells with EBV and the expression of EBV viral genes. When cells were exposed to both EBV and aflatoxin B1, they expressed even higher levels of CCL22; this indicates a possible cooperation of these exposures in the first stages of the development of endemic Burkitt lymphoma.

When the researchers created models in which the expression of CCL22 was reduced, they found decreased expression of many EBV viral genes, supporting the notion that expression of CCL22 plays an important role in B-cell infection. These findings point to a new mechanism that may operate in the early stages of the development of endemic Burkitt lymphoma. They also identify novel pathways that can be targeted in drug development against this disease, which represents almost 50% of paediatric cancers in Africa and is the leading cause of cancer-related death in many countries in Africa.

Maroui MA, Odongo GA, Mundo L, Manara F, Mure F, Fusil F, et al.
Aflatoxin B1 and Epstein Barr virus-induced CCL22 expression stimulates B cell infection
PNAS, Published online 4 April 2024;
https://doi.org/10.1073/pnas.2314426121

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