Isolation of interferon-resistant variants of friend erythroleukemia cells: Effects of interferon and ouabain

Abstract

Interferon (IFN)-resistant clones of Friend leukemia cells (FLC) have been isolated by continuous growth in IFN-rich medium followed by plating in semisolid medium in the presence of 1500 U/ml of IFN. FLC variants are fully resistant to the IFN-induced antiviral state against lytic viruses (Mengo and vesicular stomatitis virus) and retrovirus (Friend-MuLV) production at least up to IFN doses 1000-fold higher than those needed to protect parental FLC. With respect to erythroid differentiation in DMSO-induced FLC it is emphasized that: (1) the FLC variant tested was also resistant to the enhancement of erythroid differentiation by low doses (15–480 U/ml) of IFN; (2) IFN doses (5000–20,000 U/ml) practically unable to reduce Friend-MuLV release and VSV yields did inhibit, instead, the erythroid differentiation of the DMSO-induced FLC variant tested almost at the same extent as with susceptible FLC. The striking dichotomy of IFN-induced antiviral versus differentiation effects suggests that different mechanisms underlie different IFN effects, the specificity of which was fully ascertained by employing pure IFN preparations. In the FLC system, treatment with ouabain does not compete IFN-induced antiviral state. Yet, two out of three variants tested were partially resistant to ouabain-induced inhibition of Friend-MuLV release while being fully susceptible to other ouabain-induced effects on FLC. In addition, an ouabain-resistant FLC variant was not resistant to IFN.