New insights into the immunomodulatory properties of poxvirus cytokine decoy receptors at the cell surface

Abstract

Poxviruses encode a set of secreted proteins that bind cytokines and chemokines as a strategy to modulate host defense mechanisms. These viral proteins mimic the activity of host cytokine decoy receptors but have unique properties that may enhance their activity. Here, we describe the ability of poxvirus cytokine receptors to attach to the cell surface after secretion from infected cells, and we discuss the advantages that this property may confer to these viral immunomodulatory proteins.

Keywords: Immune evasion; Poxvirus; chemokine; cytokine receptor; glycosaminoglycan; interferon.

Figure 1.. Poxvirus secreted immunomodulators function at the cell surface.

Viral IL-18-binding protein (vIL-18BP) and viral IFN-I-binding protein (vIFNα/βBP) are secreted from infected cells and bind their respective ligands either as a soluble form or anchored to the cell surface through glycosaminoglycan (GAG) interactions, acting in both cases as cytokine decoy receptors. Vaccinia virus complement control protein (VCP) retention at the cell surface is mediated by either GAGs (a) or the viral protein A56 (b) and binds regulatory complement proteins promoting their inactivation. A41 and M-T1 viral chemokine-binding proteins (vCKBPs) are anchored to the surface of endothelium by interacting with GAGs and simultaneously bind chemokines. A41 interacts with the chemokine GAG-binding domain (GAG BD) to disrupt the chemotactic gradient, while M-T1 interacts with the G-protein-coupled receptor (GPCR)-binding domain (GPCR BD) in the chemokine to avoid leukocyte recognition. IFN-I, interferon type I; IL-18; interleukin-18.