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*
Immunex Corporation, Seattle WA 98101; and
Department of Molecular Microbiology and Immunology, Saint Louis University, St. Louis, MO 63104
IL-18 induces IFN-
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.
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