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Epstein–Barr virus and malaria upregulate AID and APOBEC3 enzymes, but only AID seems to play a major mutagenic role in Burkitt lymphoma

Endemic Burkitt lymphoma (eBL) is characterized by an oncogenic IGH/c‐MYC translocation and Epstein–Barr virus (EBV) positivity, and is epidemiologically linked to Plasmodium falciparum malaria. Both EBV and malaria are thought to contribute to eBL by inducing the expression of activation‐induced cy...

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Detalles Bibliográficos
Autores principales: Summerauer, Andrea M., Jäggi, Vera, Ogwang, Rodney, Traxel, Sabrina, Colombo, Lorenzo, Amundsen, Eivind, Eyer, Tatjana, Subramanian, Bibin, Fehr, Jan, Mantel, Pierre‐Yves, Idro, Richard, Bürgler, Simone
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7613445/
https://www.ncbi.nlm.nih.gov/pubmed/35503749
http://dx.doi.org/10.1002/eji.202249820
Descripción
Sumario:Endemic Burkitt lymphoma (eBL) is characterized by an oncogenic IGH/c‐MYC translocation and Epstein–Barr virus (EBV) positivity, and is epidemiologically linked to Plasmodium falciparum malaria. Both EBV and malaria are thought to contribute to eBL by inducing the expression of activation‐induced cytidine deaminase (AID), an enzyme involved in the IGH/c‐MYC translocation. AID/apolipoprotein B mRNA editing catalytic polypeptide‐like (AID/APOBEC) family enzymes have recently emerged as potent mutagenic sources in a variety of cancers, but apart from AID, their involvement in eBL and their regulation by EBV and P. falciparum is unknown. Here, we show that upon inoculation with EBV, human B cells strongly upregulate the expression of enzymatically active APOBEC3B and APOBEC3G. In addition, we found significantly increased levels of APOBEC3A in B cells of malaria patients, which correlated with parasite load. Interestingly, despite the fact that APOBEC3A, APOBEC3B, and APOBEC3G caused c‐MYC mutations when overexpressed in HEK293T cells, a mutational enrichment in eBL tumors was only detected in AID motifs. This suggests that even though the EBV‐ and P. falciparum‐directed immune response triggers the expression and activity of several AID/APOBEC members, only the upregulation of AID has oncogenic consequences, while the induction of the APOBEC3 subfamily may primarily have immunoprotective functions.