CHARACTERIZATION OF BETA-R1, A GENE THAT IS SELECTIVELY INDUCED BY INTERFERON-BETA (IFN-BETA) COMPARED WITH IFN-ALPHA

We report preliminary characterization of a gene designated beta-R1, w hich is selectively expressed in response to interferon beta (IFN-beta ) compared with IFN-alpha. In human astrocytoma cells, beta-R1 was ind uced to an equivalent extent by 10 IU/mL IFN-beta or 2500 IU/mL IFN-al pha 2. To address the mechanism of this differential response, we anal yzed induction of the beta-R1 gene in fibrosarcoma cells and derivativ e mutant cells lacking components required for signaling by type I IFN s. beta-R1 was readily induced by IFN-beta in the parental 2fTGH cell line, but not by recombinant IFN-alpha 2, IFN-alpha Con1, or a mixture of IFN-alpha subtypes. IFN-alpha 8 induced beta-R1 weakly. beta-R1 wa s not induced by IFN-beta in mutant cell lines U2A, U3A, U4A, and U6A, which lack, respectively, p48, STAT1, JAK1, and STATE. U5A cells, whi ch lack the Ifnar 2.2 component of the IFN-alpha and -beta receptor, a lso failed to express beta-R1. U1A cells are partially responsive to I FN-beta and IFN-alpha 8 but lacked beta-R1 expression, indicating that TYK2 protein is essential for induction of this gene. Taken together, these results suggest that the expression of beta-R1 in response to t ype I IFN requires IFN-stimulated gene factor 3 plus an additional com ponent, which is more efficiently formed on induction by IFN-beta comp ared with IFN-alpha.