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 IFN alpha subtypes and IFN beta. These IFNs compete for binding to cell surface receptors. However, murine cells transfected with a cDNA for a human IFN alpha receptor (IFNAR) developed an antiviral response only to human IFN alpha B, but not to human IFN alpha 2 nor -beta(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 IFNs alpha 2, -alpha B and -beta 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 IFN alpha 2, -alpha B, and -beta. 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 IFN gamma signaling which is located in the region 21p to 21q22.1(2).
Hertzog
P J
PJ
Molecular Embryology and Birth Defects Laboratory, Monash Medical Centre, Clayton, Victoria, Australia.
Hwang
S Y
SY
Holland
K A
KA
Tymms
M J
MJ
Iannello
R
R
Kola
I
I
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis; D000818:Animals; D001685:Biological Factors / Q000235:genetics* / Q000502:physiology; D016466:CHO Cells; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D006224:Cricetinae; D004790:Enzyme Induction; D020022:Genetic Predisposition to Disease; D006801:Humans; D006822:Hybrid Cells; D007370:Interferon Type I / Q000502:physiology*; D008024:Ligands; D051379:Mice; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics; D012672:Semliki forest virus / Q000472:pathogenicity; D015398:Signal Transduction / Q000235:genetics*
D001685:Biological Factors; D007370:Interferon Type I; D008024:Ligands; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D015088:2',5'-Oligoadenylate Synthetase