Inhibition of Mouse Fibroblast Interferon by Gangliosides

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Abstract
Gangliosides are potent inhibitors of the antiviral activity of mouse fibroblast and other .beta.-interferons. This study compares the effects of gangliosides on antiviral and antigrowth activities of mouse fibroblast interferon and on the induction of (2''-5'')oligoadenylate synthetase, one of the enzymes implicated in the antiviral state induced by interferon. Whereas both biological effects appear to be inhibited by gangliosides in an analogous fashion, inhibition of induction of (2''-5'')oligoadenylate synthetase does not correlate with inhibition of vesicular stomatitis virus replication. Ganglioside concentrations that inhibit the interferon-induced (2''-5'')oligoadenylate synthetase to levels close to those of uninduced cells still allow for a 100- to 1000-fold reduction of viral yield. Significantly higher ganglioside concentrations are required to completely prevent the antiviral effect. This biphasic relationship between (2''-5'')oligoadenylate synthetase levels and inhibition of viral yield suggests that no or very small increases in synthetase levels are involved in inhibition of virus by 2-3 orders of magnitude.