Abstract
IL-18 induces IFN-gamma and NK cell cytotoxicity, making it a logical target for viral antagonism of host defense. We demonstrate that the ectromelia poxvirus p13 protein, bearing homology to the mammalian IL-18 binding protein, binds IL-18, and inhibits its activity in vitro. Binding of IL-18 to the viral p13 protein was compared with binding to the cellular IL-18R. The dissociation constant of p13 for murine IL-18 is 5 nM, compared with 0.2 nM for the cellular receptor heterodimer. Mice infected with a p13 deletion mutant of ectromelia virus had elevated cytotoxicity for YAC-1 tumor cell targets compared with control animals. Additionally, the p13 deletion mutant virus exhibited decreased levels of infectivity. Our data suggest that inactivation of IL-18, and subsequent impairment of NK cell cytotoxicity, may be one mechanism by which ectromelia evades the host immune response.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding, Competitive / immunology
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COS Cells
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Cytotoxicity, Immunologic*
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Ectromelia virus / growth & development
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Ectromelia virus / immunology*
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Ectromelia virus / metabolism
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Female
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Immunosuppressive Agents / immunology
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Immunosuppressive Agents / metabolism*
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Injections, Intraperitoneal
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Interleukin-18 / antagonists & inhibitors
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Interleukin-18 / metabolism*
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Interleukin-18 Receptor alpha Subunit
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / virology
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Lymphocyte Activation
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Protein Binding / immunology
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Receptors, Interleukin / antagonists & inhibitors
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-18
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Viral Proteins / administration & dosage
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Viral Proteins / immunology
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Viral Proteins / metabolism*
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Viral Proteins / physiology
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Virus Replication
Substances
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Il18r1 protein, mouse
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Immunosuppressive Agents
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Interleukin-18
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Interleukin-18 Receptor alpha Subunit
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Receptors, Interleukin
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Receptors, Interleukin-18
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Viral Proteins