AN EPSTEIN-BARR VIRUS IMMORTALIZATION ASSOCIATED GENE SEGMENT INTERFERES SPECIFICALLY WITH THE IFN-INDUCED ANTI-PROLIFERATIVE RESPONSE IN HUMAN B-LYMPHOID CELL-LINES

Immortalization of human B-lymphocytes by Epstein-Barr virus (EBV) is associated with a decreased anti-proliferative response to interferon (IFN). In the present investigation we show that the resistance to the anti-proliferative effect of IFN class I on certain EBV-carrying Burkitt lymphoma cell lines is connected to the presence of the EBNA-2 gene and parts of the EBNA-5 gene of the EBV genome. Transfection of the genomic segment comprising these open reading frames into an IFN-sensitive lymphoma cell line demonstrated that it is sufficient to make cells resistant towards the anti-proliferative effect of IFN class I. Expression of the EBNA-2 gene seems to be correlated with the IFN-resistant phenotype. The antiviral function of IFN, as tested by inhibition by vesicular stomatitis virus (VSV) infection, and the IFN-receptor binding are not suppressed. The present results suggest that the neutralization of the anti-proliferative effect of IFN-α is involved in the EBV-mediated immmortalization of B-cells and that the anti-proliferative action of IFN class I does not necessarily recruit the same mechanism as the antiviral effect.