Burkitt lymphoma (BL), which arise from germinal centre B cells (GCB), is an aggressive non Hodgkin B-cell lymphoma. The hallmark of nearly all BL tumours is the chromosomal translocation between the MYC gene and one of the immunoglobulins (Ig) heavy or light chain loci. In accord to the World Health Organization (WHO), BL can be classified into three forms which differ in geographic distribution, clinical presentation, and Epstein–Barr virus (EBV) association: endemic (eBL), sporadic (sBL) and HIV?associated-BL. The association with EBV is highly variable, with more than 90% of the endemic cases and near 30% of HIV?associated tumours linked to EBV. The sporadic form is rarely associated to EBV, with only 10-15% cases diagnosed as EBV-positive. The majority of BL tumours express a latency type I, characterized by the expression of only EBNA1, EBV-encoded-BART miRNAs and the non-coding EBER-1 and EBER-2. However, other latent and lytic transcripts such BILF1 have been reported in a subset of BL cases. While it is well known that EBV has a significant impact on the BL pathogenesis, the function of these virus transcripts remains largely undefined. Here we have identified a novel role for the EBV-encoded-BILF1, a constitutively active viral G-protein coupled receptor that is transforming in NIH3T3 cells and which can induce tumours in nude mice. High throughput Q-PCR assay and RNA in situ hybridization revealed that BILF1 is expressed by most tumour cells of a subset of eBL. Furthermore, BILF1-expressing cells did not express the immediate-early EBV gene, BZLF1, indicating they are latently infected. Moreover, when expressed in primary human GC B cells, the progenitors of eBL, BILF1 induced a transcriptional programme that recapitulated the aberrant transcriptional programme characteristic of primary eBL. Conclusion: BILF1 induces an oncogenic transcriptional programme that could be important for the pathogenesis of a subset of eBL.

Lucia Mundo is a Marie Curie Fellow at the University of Limerick, Ireland, and Professor Adjunct in Molecular Pathology at the University of Nairobi, Kenya. His research is focused on novel insights into the pathogenesis of virus-associated malignancies for the development of new therapies. Mundo has contributed several important discoveries in the field: the first description of a non-canonical EBV-latency program in non-Hodgkin lymphomas (Abate et al. PLoS Pathogens, 2015); the first documented evidence of EBV in-situ in primary tumours classified as virus-negative (Mundo et al., Frontiers in Microbiology, 2017; Mundo et al, Modern Pathology, 2020; Infectious Agents and Cancer, 2022), the impact of BILF-1, a poorly studied gene with a great target therapy potential