title: Orf virus interleukin-10 inhibits cytokine synthesis in activated human THP-1 monocytes, but only partially impairs their proliferation.
abstract: The sheep parapoxvirus orf virus (ORFV) induces acute, pustular skin lesions in humans. ORFV encodes an orthologue of interleukin-10 (IL-10) that, whilst it closely resembles ovine IL-10 (91 % amino acid identity), shows only 75 % amino acid identity to human IL-10 (hIL-10). The anti-inflammatory potential of ORFV IL-10 in human ORFV infection was investigated by examining its immunosuppressive effects on THP-1 monocytes. ORFV IL-10 and hIL-10 were shown to have equivalent inhibitory effects on the synthesis of proinflammatory cytokines in lipopolysaccharide-activated monocytes, but differed in their abilities to inhibit monocyte proliferation. Structural modelling of ORFV IL-10 revealed differences from hIL-10 in residues predicted to interact with IL-10 co-receptor 2 (IL-10R2), whereas there were very few differences in the residues predicted to interact with IL-10R1. These findings suggest that the partial ability of ORFV IL-10 to inhibit THP-1 monocyte proliferation may be due to the absence of critical residues that mediate the interaction with human IL-10R2.
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Lyn
authors.initials: L
authors.lastname: Wise
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Catherine
authors.initials: C
authors.lastname: McCaughan
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Chee Keong
authors.initials: CK
authors.lastname: Tan
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Mercer
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fleming
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology; D016753:Interleukin-10 / Q000737:chemistry / Q000276:immunology*; D008070:Lipopolysaccharides; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology* / Q000276:immunology*; D009923:Orf virus / Q000737:chemistry / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D014764:Viral Proteins; D016753:Interleukin-10