A gene on human chromosome 21 located in the region 21q22.2 to 21q22.3 encodes a factor necessary for signal transduction and antiviral response to type I interferons

The type I interferons (IFNs) are a family of multifunctional cytokines which includes the 15 IFNα subtypes and IFNβ. These IFNs compete for binding to cell surface receptors. However, murine cells transfected with a cDNA for a human IFNα receptor (IFNAR) developed an antiviral response only to human IFNαB, but not to human IFNα2 nor -β(1). In this study we show, using a panel of CHO-human chromosome 21 hybrid cell lines which all express IFNAR, that only those containing the region 21q22.2 to 21q22.3 transduce signals for IFN responses. Two such hybrid cell lines responded to IFNsα2, - αB and -β by induction of 2'-5' oligoadenylate synthetase and resistance to viral infection. Other hybrid cell lines, that lacked the region 21q22.2-3, failed to transduce signals as above; even though they expressed IFNAR and bound human IFNα2, -αB, and -β. These data demonstrate that a gene(s) located in the region 21q22.2-3 encodes a factor(s) which is necessary for signaling but does not influence ligand binding. This factor is not the cofactor required for IFNγ signaling which is located in the region 21p to 21q22.1(2).