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 targe t for viral antagonism of host defense. We demonstrate that the ectromelia poxvirus p13 protein, bearing homology to the mammalian IL-18 binding prote in, binds IL-18, and inhibits its activity in vitro. Binding of IL-18 to th e viral p13 protein was compared with binding to the cellular IL-18R, The d issociation 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 mu tant of ectromelia virus had elevated cytotoxicity for YAC-1 tumor cell tar gets compared with control animals. Additionally, the p13 deletion mutant v irus exhibited decreased levels of infectivity. Our data suggest that inact ivation of IL-18, and subsequent impairment of NK cell cytotoxicity, may be one mechanism by which ectrometia evades the host immune response.