2′,5′-Oligoadenylate Synthetase-Uninducible Alpha/Beta-Interferon-Resistant Friend Cells Develop an Antiviral State when Permeabilized with Lysolecithin and Treated with 2′,5′-Oligoadenylate Oligomers

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Abstract
Variant sublines of Friend erythroleukemia cells (FLC) that do not respond to alpha/ beta-interferon (IFN-α/β) by developing an antiviral state but respond partially to IFN-γ with an induced antiviral state, lack the ability to induce the 2′,5′-oligoadenylate (2-5A) synthetase pathway. Exposure of wild-type and variant cells to exogenous 2-5A oligomers made permeable with lysolecithin resulted in 50-70% inhibition of protein synthesis. Further, the replication of vesicular stomatitis virus in IFN-resistant 2-5A synthetase-deficient FLC exposed to 2-5A trimer was inhibited to the same extent as in wild-type cells. Last, a significant cleavage of ribosomal RNA was observed in samples of total RNAs extracted from variant and wild-type permeabilized FLC, but only if they were exposed to 2-5A. These data are compatible with the conclusion that (i) the activation of the 2-5A-dependent endoribonuclease is not impaired in the variant cells, and (ii) the uninducibility of 2-5A synthetase can be bypassed by exogenously introducing its products, which leads to the establishment of a bona fide antiviral state.