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J Gen Virol 69 (1988), 3113-3120; DOI 10.1099/0022-1317-69-12-3113
© 1988 Society for General Microbiology
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Antiviral Activity of Tumour Necrosis Factor. Synergism with Interferons and Induction of Oligo-2',5'-adenylate Synthetase

Jürgen Mestan1, Manfred Brockhaus2, Holger Kirchner1 and Helmut Jacobsen1

1 Institute of Virus Research, German Cancer Research Center, D-6900 Heidelberg, F.R.G.
2 Hoffmann-LaRoche AG, Basel, Switzerland

Tumour necrosis factor (TNF) induces antiviral activity in HEp-2 cells. Virus yield reduction assays with vesicular stomatitis virus as challenging 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 TNF with low concentrations of either interferon (IFN)-beta1 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 2–5AS by TNF could be shown to be an indirect event that was sensitive to an antiserum against natural IFN-beta1.

Keywords: oligo-2',5'-adenylate synthetase, interferon (IFN-beta, -{gamma}), tumour necrosis factor

Received 4 May 1988; accepted 15 August 1988.


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