REGULATION OF THE INTERFERON-INDUCIBLE IFI-78K GENE, THE HUMAN EQUIVALENT OF THE MURINE MX GENE, BY INTERFERONS, DOUBLE-STRANDED-RNA, CERTAIN CYTOKINES, AND VIRUSES
REGULATION OF THE INTERFERON-INDUCIBLE IFI-78K GENE, THE HUMAN EQUIVALENT OF THE MURINE MX GENE, BY INTERFERONS, DOUBLE-STRANDED-RNA, CERTAIN CYTOKINES, AND VIRUSES
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DOI：
10.1128/jvi.63.6.2616-2622.1989
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发表时间：
1989-06-01
影响因子：
5.4
通讯作者：
HORISBERGER, MA
中科院分区：
文献类型：
--
作者：
GOETSCHY, JF;ZELLER, H;HORISBERGER, MA
编码78，000 Mr的人蛋白质p78的干扰素诱导基因（IFI-78 K基因）相当于编码Mx蛋白的小鼠Mx基因。IFI-78 K基因与α/β干扰素（IFN-α/IFN-γ）一起位于21号染色体上。beta.）受体的p78蛋白是重要的，因为它可能参与对流感病毒的抵抗。用p78 mRNA的cDNA探针和p78蛋白的特异性单克隆抗体在人二倍体细胞中研究了IFI-78 K基因的调控。IFI-78 K基因是一种正常静止的基因，受IFN-α转录调节，并且其诱导不需要蛋白质合成。在连续测定中测量的转录速率迅速但短暂地增加。p78 mRNA表达水平在8h内逐渐升高，随后缓慢下降。在未处理的细胞中检测不到的p78蛋白累积达16小时，并且在加入IFN-α后其量保持稳定至少36小时。细胞因子如肿瘤坏死因子，白细胞介素-1 α，和白细胞介素-1 β。在与IFN-α相当的浓度下激活IFI-78 K基因。然而，这些细胞因子的基因激活需要蛋白质合成。Poly（rI）-Poly（rC）直接在转录水平诱导IFI-78 K基因，而不需要蛋白质合成。纽卡斯尔病病毒、流感病毒和较小程度的水泡性口炎病毒也在没有任何蛋白质合成的情况下诱导IFI-78 K基因。通过用IFN-γ预处理细胞，病毒对转录的诱导显著增强。（其本身是IFI-78 K基因的不良诱导物），导致在感染过程中p78蛋白的积累;这表明IFN-γ在病毒感染时编程细胞以完全抗病毒活性。
The interferon-inducible gene (IFI-78K gene) that codes for a human protein, p78, of 78,000 Mr is the equivalent of the mouse Mx gene encoding Mx protein. The IFI-78K gene is located on chromosome 21 together with the alpha/beta interferon (IFN-.alpha./.beta.) receptor. The p78 protein is important since it may be involved in resistance to influenza viruses. The regulation of the IFI-78K gene was studied in human diploid cells by using a cDNA probe to p78 mRNA and specific monoclonal antibodies to p78 protein. The IFI-78K gene, a normally quiescent gene, is transcriptionally regulated by IFN-.alpha., and its induction does not require protein synthesis. The rate of transcription measured in a run-on assay increased rapidly but transiently. The level of p78 mRNA increased up to 8 h, declining slowly afterwards. The p78 protein, undetectable in untreated cells, accumulated up to 16 h, and its amount remained stable for at least 36 h after the addition of IFN-.alpha.. Cytokines such as tumor necrosis factor, interleukin-1.alpha., and interleukin-1.beta. activated the IFI-78K gene at concentrations comparable to that of IFN-.alpha.. However, gene activation by these cytokines required protein synthesis. Poly(rI)-poly(rC) induced the IFI-78K gene directly at the transcriptional level without requirement for protein synthesis. Newcastle disease virus, influenza virus, and to a lesser extent vesicular stomatitis virus also induced the IFI-78K gene in the absence of any protein synthesis. Induction of transcription by viruses was markedly enhanced by pretreatment of cells with IFN-.gamma. (which by itself is a poor inducer of the IFI-78K gene), resulting in accumulation of p78 protein during the course of infection; this suggests that IFN-.gamma. programs cells to full antiviral activity upon virus infection.