Treatment of the Burkitt lymphoma-derived cell line Daudi with highly purified human interferon-α (IFN-α) increased up to 100-fold the number of cells expressing Epstein—Barr virus (EBV)-determined early antigen (EA) without inducing the synthesis of virus capsid antigen (VCA), a late virus function. The increase in the number of EA-positive cells was proportional to interferon concentration up to 104 international units (IU)/ml. Treatment of Daudi cells with the same number of units of either partially purified (sp. act. 106 IU/mg protein) or electrophoretically pure (sp. act. 2 × 108 IU/mg protein) IFN-α both gave a similar increase in EA expression, strongly suggesting that the effects observed were indeed due to interferon. Furthermore, treatment of relatively interferon-insensitive Raji cells with IFN-α (1 to 104 IU/ml) had no significant effect on either spontaneous or 5-iodo-2′-deoxyuridine (IdUrd)-induced expression of EA or VCA. Human IFN-β also enhanced the expression of EBV EA in Daudi cells. In contrast, when the latent EBV present in Daudi cells was activated to enter into a replicative cycle, either by induction with IdUrd or by superinfection with the non-transforming P3HR1 strain of EBV, then treatment with human IFN-α caused a marked inhibition of EA expression. Our results suggest that interferon can exert a differential action on virus replication depending upon the state of the virus genome within the cell.
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