Epstein–Barr virus BZLF1 gene polymorphisms: malignancy related or geographically distributed variants?

The ubiquitous Epstein–Barr virus (EBV) is related to the development of several lymphoid and epithelial malignancies and is also the aetiological agent for infectious mononucleosis (IM). BZLF1, an immediate early gene, plays a key role in modulating the switch from latency to lytic replication, hence enabling viral propagation. Polymorphic variations in the coded protein have been studied in other geographical regions in a search for viral factors that are inherent to malignancies and differ from those present in benign infections. In the present study, in samples of paediatric patients with benign IM and paediatric patients with malignant lymphomas, we detected previously described sequence variations as well as distinctive sequence polymorphisms from our region. By means of phylogenetic reconstruction, we characterized new phylogenetically distinct variants. Moreover, we described an association between specific variants and the studied pathologies in our region, particularly variant BZLF1-A2 with lymphomas and BZLF1-C with IM. Additionally, length polymorphisms within intron 1 were also assessed and compared between pathologies resulting in an association between 29-bp repeated units and lymphomas. In conclusion, this is the first report to characterize BZLF1 gene polymorphisms in paediatric patients from our geographical region and to suggest the association of these polymorphisms with malignant lymphomas.