Esters of phosphonopropionic and phosphonoacetic acids: Effect on synthesis of Epstein-Barr virus (EBV) antigens and on transformation of cord blood lymphocytes by EBV

Cell cytotoxicity, inhibition of synthesis of Epstein-Barr virus (EBV) viral capsid antigen (VCA), nuclear antigen (EBNA) ann and of human cord blood lymphocytes (CBL) by EBV, were studied using the disodium salt of phosphonoacetic acid (PAA), ethyl diethyl-phosphonoacetate (Et-PAA) and two derivatives of phosphonopropionic acid: ethyl diethyl-2-phosphonoprionate (Et-2-PPA) and ethyl diethyl-3-phosphonoprionate (Et-3-PPA). These substances were tested on EBV producing cell lines, B.95-8 and P3HR1. VCA and EBNA synthesis were determined by immunofluorescence and transformation of CBL by ³H-thymidine uptake. Up to 100 μg/ml of PAA were not toxic to 2.10 ⁵ cells. Et-PAA, Et-2-PPA and Et-3-PPA were nontoxic at concentrations up to 2000 μg/ml. PAA inhibited 82.05% of EBV VCA synthesis at a concentration of 50 μg/ml. Et-PAA inhibited 47.01% of VCA at a concentration of 100 μg/ml and 78.09% at a concentration of 2000 μg/ml. Et-2-PPA inhibited 41.04% of VCA at 100 μg/ml and 80.87% when used at 2000 μg/ml. Et-3-PPA inhibited 35.06% of VCA at 100 μg/ml and 69.92% at 2000 μg/ml. Removal of the substances restored VCA synthesis. EBNA synthesis was not affected by these substances. PAA completely inhibited the transformation of human CBL by EBV at a concentration of 100 μg/ml. Et-PAA at a concentration of 2000 μg/ml completely inhibited ³H-thymidine uptake. Et-2-PAA was less effective whereas Et-3-PAA had almost no effect at the same concentration.