Interferon-induced expression of different genes is mediated by distinct regulatory pathways

Interferons (IFNs) regulate the expression of multiple genes and the regulatory sequences associated with several of these genes have been identified. How cell-surface IFN receptors communicate with such regulatory elements is as yet unknown. We have characterized the IFN responses of a mutant murine cell line (Ltk-aprt-) which is unable to mount an antiviral response when treated with IFN-beta. In contrast to its inability to activate antiviral pathways in these cells, IFN-beta inhibits their growth to the same level as observed in their parental L-929 line which is fully responsive to IFN, suggesting that distinct pathways account for antiviral and cytostatic responses. In agreement with this, Northern blot and nuclear run-on analyses show that the induction of transcription of three distinct genes (2,5(A) synthetase, BS-I-150, and BS-II-4) is blocked in Ltk-aprt- cells whereas another gene (I-8) is activated normally. Our results show that the defective responses observed in this cell line are not due to a nonfunctional IFN-beta cell-surface receptor and suggest that multiple pathways exist between the receptor and upstream gene regulatory elements.