Epstein-Barr virus: transformation of lymphocytes separated by size or exposed to bromodeoxyuridine and light.

Experiments designed to assess the physiological state of cells susceptible to transformation by Epstein-Barr virus (EBV) indicated that transformation does not require cellular DNA synthesis at the time of virus exposure and that a resting lymphocyte can be the target cell. The following results support this conclusion: Lymphocyte preparations from different human umbilical cords vary in extent of spontaneous DNA synthesis, but EBV-induced transformation is independent of this variation. Increases in spontaneous DNA synthesis which occur after several days in culture are not accompanied by increased cell sensitivity to transformation. Transformation occurs in highest frequency in partially purified cell subpopulations with low levels of DNA synthesis. Conversely, lymphocyte subpopulations with high rates of spontaneous DNA synthesis are relatively refractory to transformation. The fraction of cells transformed by EBV (which we estimate to be about 10% after correction for plating efficiency) exceeds the fraction in DNA synthesis at the time of virus exposure (less than 1%). Treatment of cells with bromodeoxyuridine (BrdU) followed by light before virus exposure does not impair the ability of EBV to stimulate DNA synthesis in human leukocytes or to transform marmoset leukocytes. However BrdU-light treatment is inhibitory to transformation if treatment is delivered about 24 hr after virus exposure or thereafter.