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.
Gessani
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Department of Biological Sciences, State University of New York, Albany.
Johnson
S E
SE
McCandless
S
S
Baglioni
C
C
D000998:Antiviral Agents; D004351:Drug Resistance; D004686:Encephalomyocarditis virus / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000998:Antiviral Agents; D007370:Interferon Type I; D015347:RNA Probes; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D007372:Interferons