616 Epstein - Barr Virus

A subfraction of h u m a n blood lymphocytes can lyse certain established cell lines in tissue culture in short-term assays (1-4). The system is similar to the natural killer (NK) x cell system in rats and mice (5, 6). Unlike cytotoxic T cells directed against virally determined antigens or haptens, N K cells do not appear to be under any major histocompatibil i ty complex restriction (7). The N K effect is exerted by a subset within the T-cell lineage (8-10). Most, but not all of them, carry Fc receptors (8, 11, 12) and some carry C3 receptors as well (12, 13). The panel of highly NK-sensitive cell lines in men and mice shows a somewhat erratic pattern. T cell-derived h u m a n lymphoid lines are often more sensitive than B cell-derived lines. N K activity in mice was found to increase after virus infection, t reatment of the effector cells with interferon or interferon inducers, and tumor-cell inoculation (14-16). Several recent reports suggest that viral infection of the target cells increases their N K sensitivity (17, 18). Highly NK-act ive nude mice were found to reject persistently virus-infected tumor cells, in contrast to their noninfected counterparts (19), this rejection was at t r ibuted to N K cells. It is thus conceivable, and even likely, that N K cells play a role in restricting viral infections by at tacking virally infected cells and nipping them in the bud, as it were. Although the evidence for such an effect is highly suggestive, it is far from conclusive. This paper addresses itself to the question of whether N K cells may play a role in restricting the spread of a virus that has prolonged latency as a major part of its natural life cycle, with only occasional entry of the virus-carrying cells into the productive cycle. I f N K cells play any restrictive role in limiting virus spread, it could be expected that they would kill cells that have already entered the cycle more efficiently than cells that carry the viral genome in a latent state. Epstein-Barr virus (EBV), a lymphotropic herpesvirus in man, appears to be particularly well suited for the s tudy of this question. In pr imary infection, as it occurs in infectious mononucleosis, it infects B lymphocytes and converts them into Epstein-