The mutually successful and essentially harmonious relationship of the Epstein-Barr virus (EBV) with our species stems from the resolution of two apparent contradictions. First, EBV is the most highly transforming virus known in any species, but it causes no disease in the vast majority of all infected individuals. In a relatively small minority, it causes a self-limiting disease, mononucleosis. Second, EBV-infected B lymphocytes are highly immunogenic for autologous T cells. They elicit vigorous T cell proliferation responses and generate highly cytotoxic killer cells, called cytotoxic T lymphocytes (CTLs). These interactions between autologous T and B cells are as intense as the allogeneic interactions across major histocompatibility barriers. Nevertheless, the virus is not eliminated from the hemopoetic system. Actually, it persists in the B lymphocyte fraction itself.

The resolution of these two paradoxes is closely related. The high immunogenicity of the EBV-transformed immunoblasts invites immunological surveillance against their unlimited growth. The persistence of the virus in the B lymphocyte fraction is dependent on the down-regulation of all growth transformation-associated viral proteins, except Epstein-Barr nuclear antigen 1 (EBNAl). This protein may be indispensable, owing to its role in maintaining the viral episomes (Yates et al., 1985). Current evidence is consistent with the possibility that EBNAl may not be able to provoke a CTL response.