The effect of inhibitors of RNA (actinomycin D, Act. D) and protein synthesis (cycloheximide, CH) on induction of Epstein-Barr virus (EBV) antigens by the tumour promoter TPA and by EBV superinfection has been analysed. The data indicate that (i) concomitant treatment of cells with Act. D and TPA leads to complete suppression of virus antigen induction. Subsequent treatment of the cells with Act. D after prior exposure to TPA results in some virus antigen induction, the amount depending on the time of TPA treatment. (ii) Simultaneous treatment of the cells with TPA and CH blocks antigen expression completely. Removal of the inhibitor results in antigen expression at a comparable rate to that of CH-untreated cells. (iii) If CH treatment is followed by addition of Act. D, virus antigen induction by TPA is completely inhibited. In contrast, superinfection of the cells with P3HR-1 EBV in the presence of CH for the same period followed by removal of the inhibitor and addition of Act. D leads to virus antigen expression by 3 h after Act. D addition. (iv) Concomitant treatment with CH and TPA followed by addition of either iododeoxyuridine or n-butyric acid results in ‘superinduction’. Virtually all cells exhibit EBV-specified antigens. This implies that induction of virus antigens by tumour promoters requires the synthesis of a specific RNA, that this RNA increases in concentration during the induction period and that the same RNA is not required for EBV transcription after exogenous infection.
BisterK.,
YamamotoN.,
Zur HausenH.1979; Differential inducibility of Epstein-Barr virus in cloned Raji cells. International Journal of Cancer 23:818–825
FresenK. O.,
Zur HausenH.1976; Establishment of EBNA-expressing cell lines by infection of Epstein-Barr virus (EBV)-genome-negative human lymphoma cells with different EBV strains. International Journal of Cancer 17:161–166
FresenK. O.,
ChoM.-S.,
Zur HausenH.1978; Recovery of transforming EBV from non-producer cells after superinfection with nontransforming P3HR-1 EBV. International Journal of Cancer 22:378–383
GarrenL. D.,
HowellR. R.,
TomkinsG. M.1964; A paradoxical effect of actinomycin D: the mechanism of regulation of enzyme synthesis by hydrocortisone. Proceedings of the National Academy of Sciences of the United States of America 52:1121–1126
GerberP.1972; Activation of Epstein-Barr virus by 5 bromodeoxyuridine in ‘virus-free’ human cells. Proceedings of the National Academy of Sciences of the United States of America 69:83–85
HamparB.,
DergeJ. G.,
MartosL. M.,
WalkerJ. L.1972; Synthesis of Epstein-Barr virus after activation of the viral genome in a ‘virus-negative’ human lymphoblastoid cell (Raji) made resistant to 5-bromo-deoxyuridine. Proceedings of the National Academy of Sciences of the United States of America 69:78–82
KleinG.,
DombosL.,
GothoskarB.1972; Sensitivity of Epstein-Barr virus (EBV) producer and nonproducer human lymphoblastoid cell lines to superinfection with EB-virus. International Journal of Cancer 10:44–57
SugawaraK.,
MizunoF.,
OsatoT.1972; Epstein-Barr virus associated antigens in non-producing clones of human lymphoblastoid cell lines. Nature New Biology 239:242–243
ThompsonE. B.,
GrannerD. K.,
TomkinsG. M.1970; Superinduction of tyrosine aminotransferase by actinomycin D in rat hepatoma (HTC) cells. Journal of Molecular Biology 54:159–175
TomkinsG. M.,
LevinsonB. B.,
BaxterJ. D.,
DethlefsenL.1972; Further evidence for posttranscriptional control of inducible tyrosine aminotransferase synthesis in cultured hepatoma cells. Nature New Biology 239:9–14
YajimaY.,
NonoyamaM.1976; Mechanism of infection with Epstein-Barr virus. I. Viral DNA replication and formation of noninfectious virus particles in superinfected Raji cells. Journal of Virology 19:187–194
Zur HausenH.,
BornkammG. W.,
SchmidtR.,
HeckerE.1979; Tumor initiators and promoters in the induction of Epstein-Barr virus. Proceedings of the National Academy of Sciences of the United States of America 76:782–785