Interferon action: role of membrane gangliosides.

The antiviral activity of human (fibroblast + leukocyte) and mouse fibroblast interferon was neutralized by preincubation with ganglioside before application to cells. Ganglioside mixtures were as effective as pure gangliosides, with no particular ganglioside specificity observed for neutralization of human interferon. Ganglioside-agarose derivatives removed human interferon from solution; interferon was eluted with buffers containing urea, sodium dodecyl sulfate, and mercaptoethanol. Ganglioside-deficient transformed mouse cell lines were relatively insensitive to interferon action. Treatment of such cells with ganglioside led to an increase in membrane ganglioside content and in two of three cell lines to an increase in cell sensitivity to mouse interferon; in mouse SVS AL/N and TAL/N cells, GM₂, GT₁, and a mixture of crude gangliosides were effective whereas GM₁ and GD_1a were without effect. The interferon sensitivity of untransformed cells, which failed to take up appreciable ganglioside, was not increased by treatment with exogenous ganglioside; the sensitivity of one GM₁-deficient transformed cell line ($\text{K-Balb}\text{C-3T3}$) was not increased by pretreatment with ganglioside. These results indicate an interaction between gangliosides and several types of interferon and suggest a role for membrane gangliosides in the antiviral action of interferon.