Differential responsiveness of a splice variant of the human type I interferon receptor to interferons

Abstract

Chinese hamster ovary cells containing the yeast artificial chromosome F136C5 (αYAC) respond to all type I human interferons including IFN-αA, IFN-β, and IFN-ω. The αYAC contains at least two genes encoding interferon-α receptor (IFN-αR) chains that are required for response to type I human interferons: Hu-IFN-αR1 and Hu-IFN-αR2. We previously isolated a splice variant of the Hu-IFN-αR1 chain designated Hu-IFN-αR1s. Chinese hamster ovary cells containing a disrupted αYAC, which contains a deletion in the human IFNAR1 gene, were transfected with expression vectors for the Hu-IFN-αR1 and Hu-IFN-αR1s chains. With these cells, two type I interferons have been identified which can interact with the splice variant (Hu-IFN- αR1s) and with the Hu-IFN-αR1 chains: Hu-IFN-αA and IFN-ω. Two other type I interferons, Hu-IFN-αB2 and Hu-IFN-αF, are capable of signaling through the Hu-IFN-αR1 chain only and cannot utilize the splice variant Hu-IFN- αR1s. Hu-IFN-αR1 and Hu-IFN-αR1s differ in that the latter is missing a single subdomain of the receptor extracellular domain encoded by exons 4 and 5 of the IFNAR1 gene. These results therefore indicate that different type I interferons require different subdomains of the Hu-IFN-αR1 receptor chain, and that the splice variant chain (Hu-IFN-αR1s) is functional.