Reversible inhibition by phosphonoacetic acid of human B lymphocyte transformation by Epstein-Barr virus

Abstract

B lymphocytes purified by immunoabsorbent chromatography from the peripheral blood lymphocytes of adults provide highly effective targets for infection and transformation by Epstein-Barr virus (EBV). Using this system, the kinetics of DNA synthesis induction due to EBV infection have been characterized. The kinetics show two phases: an early phase, lasting 3 to 4 days, the rate and absolute level of which are dependent upon multiplicity of infection; and a later phase, representing normal exponential growth, the level but not rate of which is dependent upon multiplicity of infection. The induction of DNA synthesis begins at a time (24 hr) which agrees well with the published times for the appearance of the Epstein-Barr virus nuclear antigen (EBNA). Absorption and penetration of the cells by EBV appear to require 1 to 2 hr. The induction of DNA synthesis proceeds normally during the first phase in the presence of phosphonoacetic acid (PAA; 200 μg/ml). Thereafter, DNA synthesis remains at a plateau. Blast-transformed EBNA-positive cells may be isolated from these cultures. Removal of PAA at any time up to 28 days postinfection results in resumed proliferation and outgrowth. These cells express four phenotypic properties of transformation by EBV: (1) induction of DNA synthesis, (2) EBNA expression, (3) blast transformation, and (4) immortalization (survival for at least 28 days). However, they cannot grow out. It is therefore proposed that the phenomenon of EBV infection in the presence of PAA may be termed “abortive transformation.”