The biological roles of two interferon-inducible chemokines, monokine induc
ed by gamma interferon (Mig) and cytokine responsive gene (Crg-2), in the i
mmune response against vaccinia virus (VV) and ectromelia virus (EV) infect
ions are discussed. To investigate their antiviral effects in viva, the exp
ression profiles of these chemokines during the course of VV or EV infectio
ns were first established. Mig and Crg-2 were induced in multiple organs at
high levels early after infection with VV. Both chemokines were rapidly in
duced in popliteal lymph nodes of C57BL/6 mice but nor in BALB/c mice follo
wing infection with EV Secondly recombinant vaccinia viruses (rVV) encoding
Mig or Crg-2 were constructed to investigate the immunobiology of infectio
n in athymic, nude and euthymic, normal mice. Finally the EV model in combi
nation with recombinant Mig and Crg-2 proteins was used to test their effec
ts on viral replication and immune responses in vivo. The results of these
investigations demonstrate that the mechanisms of Mig- and Crg-2-induced vi
ral clearance involve natural killer cells and interferons.