Transcription of the Interferon γ (IFN-γ)-inducible Chemokine Mig in IFN-γ-deficient Mice

MuMig or Mig (murine monokine induced by interferon γ) is a CXC chemokine whose induction is thought to be strictly dependent on interferon γ (IFN-γ). 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-γ (IFNγ^-/-), or receptors for IFN-α/β, IFN-γ, or both IFN-α/β and IFN-γ (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-γ^-/- mice, albeit at lower levels compared with infected, wild-type animals. In the DR^-/- mice and in IFN-γ ^-/- mice treated with a neutralizing antibody to IFN-αβ Mig mRNA transcripts were completely absent. Our data indicate that, in vaccinia virus-infected IFN^-/- mice, Mig mRNA expression is mediated through the interaction between IFN-γ responsive element 1 (γRE-1) and IFN-αβ-induced STAT-1 complex referred to as IFN-γ response factor 2 (γRF-2). Further, our findings support the view that γRF-2 is the IFN-α/β induced STAT-1 complex, IFN-α-activated factor. We have found that, in the absence of IFN-γ, IFN-αβ are able to induce Mig in response to a viral infection in vivo.