Induction of Epstein-Barr virus antigens and DNA-polymerase activities in P3HR-1 cell line and its subline passaged in the presence of phosphonoformate.

Lymphoblastoid cell line P3PFA was derived from P3HR-1 cells by long-term cultivation in the presence of phosphonoformate (PFA). Spontaneous production of Epstein-Barr virus antigens in PFA-selected subline was markedly reduced in comparison with the original cell line. Induction of early antigen (EA) and viral capsid antigen (VCA) syntheses with 5-iodo-2-deoxyuridine (IUDR), n-butyrate and 12-o-tetradecanoyl phorbol-13-acetate (TPA) was significantly less efficient in P3PFA than P3HR-1 cells. This was most likely associated with reduction in the number of viral genome copies per P3PFA cell that decreased more than one hundred times in comparison with P3HR-1 line. The synthesis of EA in both cell lines was not inhibited in the presence of PFA. On the other hand, PFA inhibited the synthesis of VCA by 95 and 30% in P3HR-1 and P3PFA, respectively. The relative resistance of VCA synthesis to PFA in P3PFA cells was not due to the presence of a drug-resistant virus-specific DNA-polymerase. It is noteworthy that the activity of virus-specific enzyme was markedly reduced, while cellular enzyme activity was significantly enhanced in induced P3PFA cells when compared to P3HR-1 cells treated in the same way.