The antiviral activity of tumor necrosis factor in HeLa cells is not mediated by interferons. Studies with TNF-resistant variants.

Tumor necrosis factor (TNF) has a relatively modest antiviral activity in HeLa cells, when compared to that of interferon (IFN). Addition of antisera neutralizing IFN-alpha or beta did not reduce the antiviral activity of TNF. Furthermore, we determined with a sensitive hybridization assay that less than one molecule of IFN-beta 1 mRNA could be present per TNF-treated cell. HeLa cell variants resistant to the TNF cytocidal activity were selected. These variants had TNF receptors with a dissociation constant similar to that of parental cells. Three cloned variants tested did not respond to the antiviral activity of TNF, but responded to IFN-alpha. Surprisingly, two of the variants did not respond to IFN-gamma. This suggests that the pathways mediating the cytocidal activity of TNF and the response to IFN-gamma share some common step. TNF induced transcription of IFN-beta 2 in resistant variants, indicating that this cytokine does not contribute to the antiviral activity of TNF.