Investigates interferon resistance in murine erythroleukemia cell clones, indicating novel genetic mechanisms.
Interferon (IFN)-resistant cell clones 3Cl8 and 3γR8, isolated from wild-type Friend erythroleukemia cells 745A were characterized to identify the resistance defect. The 3Cl8 cell clone is resistant to type I IFNs and sensitive to type II IFN, whereas 3γR8, derived from 3Cl8, is resistant to both type I and II IFNs. Here, we report that no activation of the JAK-STAT pathway is detected after IFN treatment of resistant cells. Interestingly, the absence of major transcripts of the IFNAR2 receptor chain has been observed in type I IFN-resistant cells, and a point mutation relative to the IFNGR2 receptor chain (β chain) has been identified in type II IFN-resistant cells, inducing a frameshift leading to premature termination of translation. In addition, we have identified a new polymorphism of the murine IFNAR1 chain and possibly the presence of a murine IFNAR2b transmembrane, non-transducing chain in 745A cells, similar to that observed in humans and differing from previous reports on other murine systems.
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