A poxvirus protein that binds to and inactivates IL-18, and inhibits NK cell response.
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.
Born
T L
TL
Immunex Corporation, Seattle WA 98101, USA.
Morrison
L A
LA
Esteban
D J
DJ
VandenBos
T
T
Thebeau
L G
LG
Chen
N
N
Spriggs
M K
MK
Sims
J E
JE
Buller
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D019556:COS Cells; D003602:Cytotoxicity, Immunologic; D004481:Ectromelia virus / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007166:Immunosuppressive Agents / Q000276:immunology / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000378:metabolism; D053724:Receptors, Interleukin-18; D014764:Viral Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D014779:Virus Replication
C508573:Il18r1 protein, mouse; D007166:Immunosuppressive Agents; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D014764:Viral Proteins