The human interferon α-receptor protein confers differential responses to human interferon-β versus interferon-α subtypes in mouse and hamster cell transfectants

Abstract

The human interferon α-receptor (IFNAR gene product or IFNαR protein) was expressed in hamster CHO cells and in mouse A9 cells. The response of the IFNαR cDNA transfectants to human IFNs was studied by measuring induction of (2′–5′) A synthetase (2′–5′ AS). In the murine cells, the IFNαR protein conferred response to the human IFN-α-8 (α-B) subtype, but not to huIFN-α-2 (α-A) or to huIFN-β. In murine huIFNαR cDNA transfectants, containing a hygromycin B resistance gene placed under the control of the 2′–5′ AS gene Interferon Response Sequence (IRS), survival and growth of the cells in the presence of hygromycin B was induced by huIFN-α-8 but not by huIFN-α-2, indicating that the effect of huIFNαR is transcriptional. In hamster CHO cells, the huIFNαR protein conferred a completely different pattern of response to human IFN subtypes. Thus, the CHO-IFNαR transfectants responded to huIFN-β by 2′–5′ AS induction as well as by activation of the ISGF3 and IRF-1 transcription factors. In contrast, the CHO-IFNαR cells showed no response to huIFN-α-8. The differential response conferred by the huIFNαR protein in the two types of rodent cells, indicates that IFN subtype recognition is influenced by another component contributed by the rodent host cell. The ability of human cells, and of human-mouse hybrid cells containing human chromosome 21, to respond to all IFN subtypes is likely to depend also on interactions of the IFNαR protein with additional receptor components.