The interferon-inducible chemokines MuMig and Crg-2 exhibit antiviral activity in vivo

MuMig (murine monokine induced by gamma interferon) and Crg-2 (cytokine res ponsive gene 2) are two murine chemokines of the CXC family that are induce d by the interferons (IFNs): MuMig specifically by IFN-gamma and Crg-2 by I FN-alpha, IFN-beta, and IFN-gamma. To investigate the biological roles of t hese chemokines, recombinant vaccinia viruses (rVVs) encoding either MuMig or Crg-2 were constructed. In vitro, the chemokine-encoding rVVs replicated to similar levels to the control virus. Athymic nude mice inoculated with 10(5) PFU or less of VV-HA-Mig or VV-HA-Crg-2 resolved the infection succes sfully whereas mice given a similar dose of the control virus VV-HA-TK died from generalized infection. nt higher doses, there was mortality in all gr oups but death was significantly delayed in mice infected with either chemo kine-encoding rVV compared with those infected with the control virus. Viru s-encoded MuMig and Crg-2 enhanced the cytolytic activity of Ng cells and s plenic cellularity by two- to threefold and resulted in significant increas es in mononuclear cell infiltration in the livers of mice. Using specific n eutralizing or depleting antibodies, we have established that the control o f rVV replication in athymic nude mice, as a consequence of virus-expressed MuMig and Crg-2, requires NK cells and IFN-alpha, IFN-beta, and IFN-gamma.