A Poxvirus Protein That Binds to and Inactivates IL-18, and Inhibits NK Cell Response

• Published in: The Journal of immunology (1950) Vol. 164; no. 6; pp. 3246 - 3254
• Main Authors: Born, Teresa L, Morrison, Lynda A, Esteban, David J, VandenBos, Tim, Thebeau, Lydia G, Chen, Nanhai, Spriggs, Melanie K, Sims, John E, Buller, R. Mark L
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-03-2000
• Subjects: Amino Acid Sequence; Animals; Binding, Competitive - immunology; COS Cells; Cytotoxicity, Immunologic; Ectromelia virus - growth & development; Ectromelia virus - immunology; Ectromelia virus - metabolism; Female; Immunosuppressive Agents - immunology; Immunosuppressive Agents - metabolism; Injections, Intraperitoneal; Interleukin 18 receptors; Interleukin-18 - antagonists & inhibitors; Interleukin-18 - metabolism; Interleukin-18 Receptor alpha Subunit; Killer Cells, Natural - immunology; Killer Cells, Natural - virology; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Molecular Sequence Data; p13 protein; poxvirus; Protein Binding - immunology; Receptors, Interleukin - antagonists & inhibitors; Receptors, Interleukin - metabolism; Receptors, Interleukin-18; Viral Proteins - administration & dosage; Viral Proteins - immunology; Viral Proteins - metabolism; Viral Proteins - physiology; Virus Replication
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.6.3246

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.