The Interferon-Inducible Chemokines MuMig and Crg-2 Exhibit Antiviral Activity In Vivo
Tóm tắt
MuMig (murine monokine induced by gamma interferon) and Crg-2 (cytokine responsive gene 2) are two murine chemokines of the CXC family that are induced by the interferons (IFNs): MuMig specifically by IFN-γ and Crg-2 by IFN-α, IFN-β, and IFN-γ. To investigate the biological roles of these 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 105PFU or less of VV-HA-Mig or VV-HA–Crg-2 resolved the infection successfully whereas mice given a similar dose of the control virus VV-HA-TK died from generalized infection. At higher doses, there was mortality in all groups but death was significantly delayed in mice infected with either chemokine-encoding rVV compared with those infected with the control virus. Virus-encoded MuMig and Crg-2 enhanced the cytolytic activity of NK cells and splenic cellularity by two- to threefold and resulted in significant increases in mononuclear cell infiltration in the livers of mice. Using specific neutralizing or depleting antibodies, we have established that the control of rVV replication in athymic nude mice, as a consequence of virus-expressed MuMig and Crg-2, requires NK cells and IFN-α, IFN-β, and IFN-γ.
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Tài liệu tham khảo
Amichay D. Gazzinelli R. T. Karupiah G. Moench T. R. Sher A. Farber J. M. The gene for chemokines MuMig and Crg-2 are induced in protozoan and viral infections in response to IFN-γ with patterns of tissue expression that suggest nonredundant roles in vivo.J. Immunol. 157 1996 4511 4520
Karupiah G. Coupar B. E. H. Andrew M. E. Boyle D. B. Phillips S. M. Mullbacher A. Blanden R. V. Ramshaw I. A. Elevated NK cell responses in mice infected with recombinant vaccinia virus encoding murine IL-2.J. Immunol. 144 1990 290 298
Mahalingam S. C. L. Tan and G. Karupiah. Unpublished data.
Mahalingam S. J. M. Farber and G. Karupiah. Unpublished data.
Pardoll D. M. Fowlkes B. J. Lew A. M. Maloy W. L. Weston M. A. Bluestone J. A. Schwartz R. H. Cooligan J. E. Kruisbeek A. M. Thymus-dependent and thymus independent developmental pathways for peripheral T cell receptor-γδ-bearing lymphocytes.J. Immunol. 140 1988 4091 4096
Rabin R. M. Park F. Liao R. Swafford D. Stephany and J. M. Farber. Unpublished data.
Salazar-Mather T. P. Ishikawa R. Biron C. A. NK cell trafficking and cytokine expression in splenic compartments after IFN induction and viral infection.J. Immunol. 157 1996 3054 3064
Svetic A. Finkelman F. D. Jian Y. C. Dieffenbach C. W. Scott D. E. McCarthy K. F. Steinberg A. D. Gause W. C. Cytokine gene expression after in vivo primary immunization with goat antibody to mouse IgD antibody.J. Immunol. 147 1991 2391 2397
Taub D. D. Sayers T. J. Carter C. R. D. Ortaldo J. R. α and β chemokines induce NK cell migration and enhance NK-mediated cytolysis.J. Immunol. 155 1995 3877 3888