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 antiproliferative 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-alpha is involved in the EBV-mediated immortalization of B-cells and that the anti-proliferative action of IFN class I does not necessarily recruit the same mechanism as the antiviral effect.
Aman
P
P
Department of Bacteriology, Karolinska Institute, Stockholm, Sweden.
von Gabain
A
A
D000956:Antigens, Viral / Q000235:genetics*; D001402:B-Lymphocytes / Q000166:cytology*; D002455:Cell Division; D002472:Cell Transformation, Viral; D004351:Drug Resistance / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens; D015870:Gene Expression; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D007370:Interferon Type I / Q000494:pharmacology*; D008223:Lymphoma; D011971:Receptors, Immunologic / Q000378:metabolism; D017471:Receptors, Interferon; D014162:Transfection; D014407:Tumor Cells, Cultured
D000956:Antigens, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D007370:Interferon Type I; D011971:Receptors, Immunologic; D017471:Receptors, Interferon