Animal models of Epstein Barr virus infection

•EBV persists in mice with reconstituted human immune system components (HIS mice).•EBV induces lymphomas with similarities to those in patients in HIS mice.•HIS mice expand the same NK cells as children upon primary EBV infection.•Early differentiated NK cells restrict lytic EBV infection in HIS mice.•T cells restrict EBV infection and tumorigenesis in HIS mice.

Epstein Barr virus (EBV) was the first human tumor virus to be described. Despite its discovery now more than fifty years ago, immune control of this virus is still not very well understood and no vaccine is available. This knowledge gap is due in part to the lack of a preclinical small animal model which can faithfully recapitulate EBV infection and immune control, and would allow testing of EBV specific vaccine candidates. With the advent of mice with reconstituted human immune system compartments (HIS mice) during the past decade this is changing. We will discuss which aspects of EBV infection and its immune control can already be modeled in HIS mice, and which shortcomings still need to be overcome in order to recapitulate the immunobiology of oncogenic EBV infection.