The Interferon-Inducible Chemokines MuMig and Crg-2 Exhibit Antiviral Activity In Vivo

Journal of Virology - Tập 73 Số 2 - Trang 1479-1491 - 1999
Suresh Mahalingam1, Joshua Μ. Farber2, Gunasegaran Karupiah1
1Host Defense Laboratory, Viral Engineering and Cytokines Group, Division of Immunology and Cell Biology, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia,1and
2Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 208922

Tóm tắt

ABSTRACTMuMig (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.

Từ khóa


Tài liệu tham khảo

10.1128/jvi.69.8.4633-4639.1995

10.1126/science.272.5270.1955

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

10.1016/0882-4010(86)90006-9

10.1159/000237207

10.1038/33340

10.1016/S0092-8674(00)81313-6

10.1126/science.270.5243.1811

10.1126/science.7667639

10.1016/0378-1119(88)90593-8

10.1126/science.8456300

10.1038/381661a0

10.1016/S0092-8674(00)81314-8

10.1038/381667a0

10.1073/pnas.87.14.5238

10.1128/mcb.12.4.1535-1545.1992

10.1006/bbrc.1993.1403

10.1126/science.272.5263.872

10.1016/S0021-9258(19)61936-8

10.1007/BF01378632

10.1126/science.7689250

10.1126/science.8456301

10.1084/jem.172.5.1495

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

10.1128/jvi.67.7.4214-4226.1993

10.1126/science.7690156

10.1006/viro.1997.8900

10.1128/JVI.72.9.7703-7706.1998

10.1002/eji.1830200123

10.1038/227680a0

10.1084/jem.185.11.2015

10.1084/jem.182.5.1301

10.1084/jem.184.3.963

10.1128/jvi.71.2.1671-1678.1997

10.1096/fasebj.11.10.9271361

Mahalingam S. C. L. Tan and G. Karupiah. Unpublished data.

Mahalingam S. J. M. Farber and G. Karupiah. Unpublished data.

10.1126/science.8009221

10.1073/pnas.89.18.8676

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.

10.1038/329545a0

10.1111/j.1600-065X.1992.tb01413.x

10.1111/j.1600-065X.1997.tb01011.x

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

10.1038/347669a0

10.1084/jem.177.6.1821

10.1016/S0021-9258(18)42719-6

10.1073/pnas.89.13.6070

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

10.1016/0092-8674(95)90076-4

10.1084/jem.177.6.1809

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

10.1016/S0021-9258(18)77222-0

10.1038/324482a0

Thông tin
Thông tin xuất bản

Journal of Virology

Tập 73 Số 2

1479-1491

Thông tin tác giả