Interleukin-18 and glycosaminoglycan binding by a protein encoded by Variola virus.
Poxvirus interleukin (IL)-18 binding proteins (IL-18BPs) are soluble decoys that inhibit the activity of IL-18. The aim of this study was to demonstrate IL-18 binding activity of the Variola virus protein D7L. D7L effectively inhibited the biological activity of IL-18 in a bioassay. We compared the affinity and kinetics of D7L and the Ectromelia virus IL-18BP, p13, for human and murine IL-18 using surface plasmon resonance and no differences were detected, indicating that the differences in amino acid sequence did not affect binding or species specificity. Both proteins had higher affinity for murine than human IL-18. This was similar to human IL-18BP and the Molluscum contagiosum virus IL-18BP, which also demonstrated higher affinity for human IL-18. The host range of Variola virus is limited to humans and thus the affinity of D7L for IL-18 does not correlate with its host range. Furthermore, we demonstrated that D7L is capable of interacting with glycosaminoglycans (GAGs) via the C terminus, while p13 is not. Importantly, D7L interacted with both GAG and IL-18 simultaneously, indicating that the binding sites were distinct.
Esteban
David J
DJ
St Louis University Health Sciences Center, Department of Molecular Microbiology and Immunology, 1402 South Grand Blvd, St Louis, MO 63104, USA.
Nuara
Anthony A
AA
St Louis University Health Sciences Center, Department of Molecular Microbiology and Immunology, 1402 South Grand Blvd, St Louis, MO 63104, USA.
Buller
R Mark L
RML
St Louis University Health Sciences Center, Department of Molecular Microbiology and Immunology, 1402 South Grand Blvd, St Louis, MO 63104, USA.
D000595:Amino Acid Sequence; D000818:Animals; D006023:Glycoproteins / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18 / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D016415:Sequence Alignment; D013045:Species Specificity; D012901:Variola virus / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D006023:Glycoproteins; D006025:Glycosaminoglycans; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D014764:Viral Proteins; C118370:interleukin-18 binding protein