CELL INTERACTION WITH A SYNTHETIC POLYNUCLEOTIDE AND INTERFERON PRODUCTION IN VITRO

The first step in interferon production by double-stranded polyribocytidylate: polyriboinosinate (poly C:I) is the binding of poly C:I to the cell surface. It can be demonstrated either at 4° or at 37°. Using radiolabeled poly C:I, cell binding of poly C:I was shown to be greatly enhanced by DEAE-dextran. A second, temperature-dependent step occurs rapidly after cell binding of poly C:I and is followed by cellular resistance to virus infection and interferon production. Study of this temperature-dependent step showed that the bulk of cell-associated poly C:I persists at the cell surface and that very little poly C:I is taken into cells during this time. Autoradiography of human fibroblasts incubated for various intervals with tritiated poly C:I at 37° showed that poly C:I is degraded in cells and that the fragments are utilized for cellular RNA synthesis. Such utilization could be blocked by treatment of cells with actinomycin D and cytidine while interferon production was not decreased. Study of the interaction of poly C:I with L cells indicated that these cells take up similar amounts of poly C:I as human fibroblasts under the same conditions but do not produce interferon in the absence of DEAE-dextran. Our findings suggest that the amount of cell-associated poly C:I required for initiation of interferon production is not the same in different cell systems and further suggest that much of the cellular uptake of poly C:I is not essential for interferon production. © 1969.