Mahalingam S, Chaudhri G, Tan C L, John A, Foster P S, Karupiah G
School of Human and Biomedical Sciences, Division of Science and Design, University of Canberra, Canberra, ACT 2601, Australia.
J Biol Chem. 2001 Mar 9;276(10):7568-74. doi: 10.1074/jbc.M005773200. Epub 2000 Oct 9.
MuMig or Mig (murine monokine induced by interferon gamma) is a CXC chemokine whose induction is thought to be strictly dependent on interferon gamma (IFN-gamma). Here we have studied the expression of this chemokine gene in various organs of mice infected with vaccinia virus. We have employed animals deficient in either IFN-gamma (IFN-gamma(-/-)), or receptors for IFN-alpha/beta, IFN-gamma, or both IFN-alpha/beta and IFN-gamma (DR(-/-)) to dissect out the role of interferons in the induction of Mig during the host response to virus infection. Our data show that Mig mRNA and protein are expressed in organs of vaccinia virus-infected IFN-gamma(-/-) mice, albeit at lower levels compared with infected, wild-type animals. In the DR(-/-) mice and in IFN-gamma(-/-) mice treated with a neutralizing antibody to IFN-alpha/beta, Mig mRNA transcripts were completely absent. Our data indicate that, in vaccinia virus-infected IFN-gamma(-/-) mice, Mig mRNA expression is mediated through the interaction between IFN-gamma responsive element 1 (gammaRE-1) and IFN-alpha/beta-induced STAT-1 complex referred to as IFN-gamma response factor 2 (gammaRF-2). Further, our findings support the view that gammaRF-2 is the IFN-alpha/beta induced STAT-1 complex, IFN-alpha-activated factor. We have found that, in the absence of IFN-gamma, IFN-alpha/beta are able to induce Mig in response to a viral infection in vivo.
MuMig或Mig（γ干扰素诱导的小鼠单核因子）是一种CXC趋化因子，其诱导被认为严格依赖于γ干扰素（IFN-γ）。在此，我们研究了这种趋化因子基因在感染痘苗病毒的小鼠各器官中的表达。我们利用缺乏IFN-γ（IFN-γ(-/-)）、IFN-α/β受体、IFN-γ受体或同时缺乏IFN-α/β和IFN-γ受体（DR(-/-)）的动物，来剖析干扰素在宿主对病毒感染的反应中诱导Mig的作用。我们的数据表明，Mig mRNA和蛋白在感染痘苗病毒的IFN-γ(-/-)小鼠的器官中表达，尽管与感染的野生型动物相比水平较低。在DR(-/-)小鼠和用抗IFN-α/β中和抗体处理的IFN-γ(-/-)小鼠中，完全没有Mig mRNA转录本。我们的数据表明，在感染痘苗病毒的IFN-γ(-/-)小鼠中，Mig mRNA表达是通过IFN-γ反应元件1（γRE-1）与IFN-α/β诱导的称为IFN-γ反应因子2（γRF-2）的STAT-1复合物之间的相互作用介导的。此外，我们的发现支持γRF-2是IFN-α/β诱导STAT-1复合物即IFN-α激活因子的观点。我们发现，在缺乏IFN-γ的情况下，IFN-α/β能够在体内对病毒感染作出反应诱导Mig。
