Organophosphorous compounds as inhibitors of EBV infection and transformation

Phosphonoformic acid trisodium salt (PF), ethyl diethyl-phosphonoformate (Et-PF), phosphonoacetic acid (PAA), ethyl diethyl phosphonoacetate (Et PAA), ethyl diethyl-2-phosphonopropionate (Et-2-PPA) and ethyl diethyl-3-phosphonopropionate (Et-3-PPA) were tested as inhibitors of EBV virus capsid antigen (VCA) synthesis in B.95-8 cells by immunofluorescence. The most effective inhibitors were: PF, inhibition of 96.74 percent of VCA synthesis at a concentration of 500 microM and PAA, inhibition of 82.05 percent of VCA synthesis at a concentration of 250 microM. Much higher concentrations of the other compounds were needed for inhibition with lower efficiency. Synthesis of EBV nuclear antigen (EBNA) was not inhibited by PF or PAA. However, only PF and PAA inhibited the transformation of human cord blood lymphocytes (CBL) by EBV, as measured by 3H-thymidine uptake, even when added 24 hours after infection. The degree of inhibition of transformation correlated with the concentration. Complete inhibition of CBL transformation by EBV was achieved by 1,000 microM PF and 500 microM PAA, which were noncytotoxic. Removal of PAA from B.95-8 cells cultivated in the presence of high concentrations of PAA for 15 weeks restored VCA synthesis without full concomitant production of transforming EBV.