Sequence and functional analysis of a homolog of interleukin-10 encoded bythe Parapoxvirus orf virus

Orf virus isa large DNA virus and is the type species of the Parapoxvirus g enus of the family Poxviridae. Orf virus infects the epithelium of sheep an d goats and is transmissible to humans. Recently we discovered a gene in or f virus that encodes a polypeptide with remarkable homology to mammalian in terleukin (IL-10) and viral encoded IL-10s of herpes viruses. The predicted polypeptide sequence shows high levels of amino acid identity to IL-10 of sheep (80%), cattle (75%), humans (67%) and mice (64%), as well as IL-10-li ke proteins of Epstein-Barr virus (63%) and equine herpes; virus (67%). The C-terminal region, comprising two-thirds of the orf virus protein, is iden tical to ovine IL-10 which suggests that this gene has been captured from i ts host sheep during the evolution of orf virus. In contrast the N-terminal region shows little homology with cellular IL-10s and in this respect rese mbles other viral IL-10s. IL-10s is a pleiotrophic cytokine that can exert either immunostimulatory or immunosuppressive effects on many cell types. I L-10 is a potent anti-inflammatory cytokine with inhibitory effects on non- specific immunity in particular macrophage function and Th1 effector functi on. Our studies so far, indicate, that the functional activities of orf vir us IL-10 are the same as ovine IL-I10 Orf virus IL-10 stimulates mouse thym ocyte proliferation and inhibits cytokine synthesis in lipopolysaccharide-a ctivated ovine macrophages, peripheral blood monocytes and keratinocytes. I nfection of sheep with an IL-10 deletion mutant of orf virus has shown that interferon-gamma levels are higher in tissue infected with the mutant viru s than the parent virus. The functional activities of IL-10 and our data on orf virus IL-10 suggest a role in immune evasion.