Abstract
Epstein–Barr virus (EBV) is a lymphotropic herpes virus associated with a variety of diseases including infectious mononucleosis, lymphoproliferative diseases, and malignant diseases such as Burkitt lymphoma and Hodgkin lymphoma. EBV is also implicated in various autoimmune diseases. Humans are the only natural host of EBV and small animal models of EBV infection have not been available, although a few new-world monkeys can be infected with the virus experimentally. Humanized mice harboring functioning human lymphocytes can be readily infected with EBV and have reproduced cardinal features associated with human EBV infection, including lymphoproliferative disease, hemophagocytic lymphohistiocytosis, erosive arthritis resembling rheumatoid arthritis, and asymptomatic persistent infection. EBV-specific T-cell responses are induced in humanized mice that protect them from uncontrolled proliferation of EBV-infected cells. Chronic active EBV infection, an EBV-associated T/NK lymphoproliferative disease, that could not be reproduced in humanized mice, has been recapitulated by xenogeneic transplantation of patient’s peripheral blood mononuclear cells to NOG mice. This chapter summarizes features of human EBV infection that were reproduced in humanized mouse models and mouse xenograft models, and shows how they have been utilized to analyze EBV pathogenesis and normal and aberrant human immune responses to the virus.
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