Infection of human B cells with Epstein-Barr virus results in the expression of somatic hypermutation-inducing molecules and in the accrual of oncogene mutations

Infection of human B cells with Epstein-Barr virus (EBV) was seen to result in activation-induced cytidine deaminase (AID) and polymerase-η (pol-η) gene expression. AID and pol-η are cellular gene products that play central roles in the DNA-modifying processes involved in immunoglobulin gene class switch recombination and somatic hypermutation. Errors in these processes can result in oncogene mutation/translocation, thereby contributing to lymphomagenesis. It was seen that EBV infected, AID, and pol-η expressing B cells accumulated mutations in cellular proto-oncogenes (BCL-6 and p53) that are known to be involved in the genesis of B cell lymphoma. The nature of the mutations seen in these oncogenes was consistent with the known activity of AID and pol-η. These findings indicate that EBV induced AID and pol-η expression, and that this was associated with oncogene mutation, providing a novel means by which EBV infection of B cells may contribute to lymphomagenesis.