Epstein Barr Virus (EBV), a gammaherpesvirus, which can primarily manifest as self-resolving infectious mononucleosis, is a well-known cause of viral complications in immunocompromised transplant patients. It is also associated with cancers like the Hodgkin’s lymphomas and post- transplant lymphoproliferative disease. It has recently been implicate in autoimmune diseases. Apart from radio and chemotherapy approaches to curtail EBV- transformed cell growth, there are no licensed targeted treatments available for EBV diseases. With recent advances in EBV-specific T cell immunotherapy, an increased interest has risen in combined cellular immunotherapy approach to combat the disease. However, the evaluation and validation of these novel immunotherapies requires homologous animal model, which is challenged by the limited tropism of the virus.
However, our lab has developed a humanized model, wherein, the EBV humanized mouse model is engrafted with CD34+ hematopoietic progenitor stem cells (HSCs) and upon reconstitution of immune system, they are infected with EBV. Contrary to mature PBMC injection in SCID mice, these do not cause graft- versus- host disease and are EBV negative universally.
This has allowed us a platform to investigate the underlying immunological, virological and serological parameters of EBV associated lymphomas and other EBV-associated autoimmune conditions. It provides a powerful resource to study viral trafficking and histopathology enabling us to demonstrate spatial configuration of immune cells in relation to EBV virus. Importantly, this model enables us to examine the temporal activity of cytotoxic lymphocytes as a therapy for EBV-associated tumours.
Most recently, evidence linking EBV and Long Covid has seen a renewed interest in EBV-associated diseases and need to understand the re- activation of latent EBV. Our study supports this multi- faceted need for a comprehensive model to study EBV infection alongside the global immune network at play, and to investigate and develop novel immunotherapies for EBV-associated conditions.