Orf virus interleukin-10 inhibits cytokine synthesis in activated human THP-1 monocytes, but only partially impairs their proliferation.
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.
Wise
Lyn
L
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
McCaughan
Catherine
C
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Tan
Chee Keong
CK
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Mercer
Andrew A
AA
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Fleming
Stephen B
SB
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
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*
D016207:Cytokines; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D014764:Viral Proteins; D016753:Interleukin-10