Sensitivity of the Transforming and Replicative Functions of Epstein-Barr Virus to Inhibition by Phosphonoacetate

Disodium, phosphonoacetate (PA), at concentrations of 50 to 200 microgram/ml, which still allowed continued growth of the EB virus-transformed B95-8 cell line on a routine culture regimen, was able to inhibit the production of virus capsid antigen and of virus particles by these cells down to very low but finite levels which persisted despite prolonged treatment. Further experiments measured the effects of these same drug concentrations on the EB virus-induced in vitro transformation of foetal cord blood lymphocytes and on the colony forming ability of already established EB virus-transformed foetal cell lines; in both types of culture, doses of PA up to and including 50 microgram/ml did not affect cell growth within the 8-week observation period, whereas doses of 100 microgram/ml and above were increasingly inhibitory. The cell lines established by EB virus-induced transformation in the continual presence of PA at 50 to 150 microgram/ml contained multiple copies of the virus genome per cell just as did the corresponding cell lines established in control medium. The results argue against the existence of any PA-sensitive event unique to the EB virus-induced transformation process.