Interferon-inducible Chemokines and Immunity to Poxvirus Infections

The biological roles of two interferon-inducible chemokines, monokine induced by gamma interferon (Mig) and cytokine responsive gene (Crg-2), in the immune response against vaccinia virus (VV) and ectromelia virus (EV) infections are discussed. To investigate their antiviral effects in vivo, the expression profiles of these chemokines during the course of VV or EV infections were first established. Mig and Crg-2 were induced in multiple organs at high levels early after infection with VV. Both chemokines were rapidly induced in popliteal lymph nodes of C57BL/6 mice but not in BALB/c mice following infection with EV. Secondly, recombinant vaccinia viruses (rVV) encoding Mig or Crg-2 were constructed to investigate the immunobiology of infection in athymic, nude and euthymic, normal mice. Finally, the EV model in combination with recombinant Mig and Crg-2 proteins was used to test their effects on viral replication and immune responses in vivo. The results of these investigations demonstrate that the mechanisms of Mig- and Crg-2-induced viral clearance involve natural killer cells and interferons.