Transcription of the interferon γ (IFN-γ)-inducible chemokine Mig in IFN-γ-deficient mice

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-/-), or receptors for IFN-alpha/beta, IFN-gamma, or both IFN-alpha/beta gamma 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, Mg mRNA expression is mediated through the interaction between IFN-gamma responsive element 1 (gamma RE-1) and IFN-alpha/beta -induced STAT-1 complex referred to as IFN-y response factor 2 (gamma RF-2). Further, our findings support the view that gamma RF-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.