A poxvirus protein that binds to and inactivates IL-18, and inhibits NK cell response
| Autor: | Nanhai Chen, M K Spriggs, Lydia G. Thebeau, R M Buller, David J. Esteban, Lynda A. Morrison, T VandenBos, T L Born, John E. Sims |
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| Rok vydání: | 2000 |
| Předmět: |
Cytotoxicity
Immunologic Ectromelia virus viruses Immunology Molecular Sequence Data Biology Lymphocyte Activation Virus Replication Binding Competitive Virus Ectromelia Mice Viral Proteins medicine Immunology and Allergy Animals Amino Acid Sequence Cytotoxicity Receptor Receptors Interleukin-18 COS cells Binding protein Interleukin-18 Receptors Interleukin medicine.disease biology.organism_classification Molecular biology Killer Cells Natural Mice Inbred C57BL Viral replication COS Cells Female Interleukin-18 Receptor alpha Subunit Immunosuppressive Agents Injections Intraperitoneal Protein Binding |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 164(6) |
| ISSN: | 0022-1767 |
| Popis: | IL-18 induces IFN-γ 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. |
| Databáze: | OpenAIRE |
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