Parapoxvirus Interleukin-10 Homologues Vary in Their Receptor Binding, Anti-Inflammatory, and Stimulatory Activities

Abstract

Homologues of interleukin (IL)-10, a pleiotropic immunomodulatory cytokine, have been identified in the Parapoxvirus genus. The first identified, Orf virus (ORFV) IL-10, greatly enhanced infection of its host, exhibiting immune modulatory effects equivalent to human IL-10. IL-10-like genes were then identified in Bovine papular stomatitis virus (BPSV), Pseudocowpox virus (PCPV), Red deerpox virus (RDPV) and Grey sealpox virus (GSPV). This study aimed to produce and characterise recombinant parapoxvirus IL-10s, then quantitatively compare their receptor binding and immunomodulatory activities. Recombinant IL-10s were expressed, purified, then characterised using bioinformatic, biochemical and enzymatic analyses. Anti-inflammatory effects were assessed in lipoteichoic acid-activated THP-1 monocytes, and stimulatory effects in MC/9 mast cells. IL-10 receptor (IL-10R)1 binding was detected in a competitive displacement assay. BPSV IL-10 inhibited production of monocyte chemoattractant protein (MCP)-1, IL-8 and IL-1β, induced mast cell proliferation, and bound IL-10R1 similarly to ORFV IL-10. PCPV IL-10 showed reduced MCP-1 inhibition, mast cell proliferation, and IL-10R1 binding. RDPV IL-10 displayed reduced inhibition of IL-8 and MCP-1 production. GSPV IL-10 showed limited inhibition of IL-1β production and stimulation of mast cell proliferation. These findings provide valuable insight into IL-10 receptor interactions, and suggest that the parapoxvirus IL-10s play similar pathogenic roles during infection of their hosts.

Temperature impacts Atlantic salmon's (Salmo salar) immunological response to infectious salmon anemia virus (ISAv).

“…The crucial role IL-10 plays in homeostasis can also be hijacked by viruses, as numerous viruses produce IL-10 homologues giving them the ability to polarize antigen presenting cell (i.e. macrophage) subtypes, as discussed above in bacteria, to allow for survival and reduced adaptive immune recognition [35] . In our case, upregulation of IL-10 may have helped control the inflammation response after the initial onset of infection and protected against the more severe acute mortality observed at 20 °C, but may have led to improved survival for the virus and greater chronic mortality observed at this temperature.…”