Antiviral Activity of Tumour Necrosis Factor. Synergism with Interferons and Induction of Oligo-2',5'-adenylate Synthetase

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Abstract
Tumour necrosis factor (TNF) induces antiviral activity in HEp-2 cells. Virus yield reduction assays with vesicular stomatitis virus as challengeing virus demonstrated that the antiviral state was more pronounced in confluent cultures under low serum conditions. A significant enhancement of the antiviral state was obtained by combining TNA was low concentrations of either interferon (IFN)-.beta.1 or IFN-.gamma.. The reduction in virus yield was significantly higher than that expected from summation of the independent antiviral activities of either substance alone, i.e. TNF and IFN acted synergistically as antiviral agents. Synergism of TNF with IFN-.beta. or IFN-.gamma. appeared to be mediated by different pathways since different requirements for pretreatment and different effects on oligo-2'',5''-adenylate synthetase (2-5AS) induction were observed. Induction of 2-5 AS by TNF could be shown to be an indirect event that was sensitive to an antiserum against natural IFN-.beta.1.