Abramovich C, Chebath J, Revel M
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
Cytokine. 1994 Jul;6(4):414-24. doi: 10.1016/1043-4666(94)90066-3.
The human interferon alpha-receptor (IFNAR gene product or IFN alpha R protein) was expressed in hamster CHO cells and in mouse A9 cells. The response of the IFN alpha R cDNA transfectants to human IFNs was studied by measuring induction of (2'-5') A synthetase (2'-5' AS). In the murine cells, the IFN alpha R protein conferred response to the human IFN-alpha-8 (alpha-B) subtype, but not to huIFN-alpha-2 (alpha-A) or to huIFN-beta. In murine huIFN alpha R 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-alpha-8 but not by huIFN-alpha-2, indicating that the effect of huIFN alpha R is transcriptional. In hamster CHO cells, the huIFN alpha R protein conferred a completely different pattern of response to human IFN subtypes. Thus, the CHO-IFN alpha R transfectants responded to huIFN-beta by 2'-5' AS induction as well as by activation of the ISGF3 and IRF-1 transcription factors. In contrast, the CHO-IFN alpha R cells showed no response to huIFN-alpha-8. The differential response conferred by the huIFN alpha R 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 IFN alpha R protein with additional receptor components.
人α干扰素受体（IFNAR基因产物或IFNαR蛋白）在仓鼠CHO细胞和小鼠A9细胞中表达。通过测量（2'-5'）寡腺苷酸合成酶（2'-5'AS）的诱导情况，研究了IFNαR cDNA转染细胞对人干扰素的反应。在鼠细胞中，IFNαR蛋白赋予了对人IFN-α-8（α-B）亚型的反应能力，但对huIFN-α-2（α-A）或huIFN-β无反应。在含有置于2'-5'AS基因干扰素反应序列（IRS）控制下的潮霉素B抗性基因的鼠huIFNαR cDNA转染细胞中，huIFN-α-8可诱导细胞在潮霉素B存在下存活和生长，而huIFN-α-2则不能，这表明huIFNαR的作用是转录性的。在仓鼠CHO细胞中，huIFNαR蛋白赋予了对人干扰素亚型完全不同的反应模式。因此，CHO-IFNαR转染细胞通过2'-5'AS诱导以及ISGF3和IRF-1转录因子的激活对huIFN-β产生反应。相比之下，CHO-IFNαR细胞对huIFN-α-8无反应。huIFNαR蛋白在两种啮齿动物细胞中赋予的不同反应表明，干扰素亚型识别受啮齿动物宿主细胞贡献的另一种成分影响。人细胞以及含有人类21号染色体的人-鼠杂交细胞对所有干扰素亚型产生反应的能力可能也取决于IFNαR蛋白与其他受体成分的相互作用。
