title: Attenuation of innate immunity by cytomegalovirus IL-10 establishes a long-term deficit of adaptive antiviral immunity.
abstract: Human cytomegalovirus (HCMV) and many other pathogens exploit the IL-10 pathway, as part of their infectious cycle, either through their own encoded IL-10 (hcmvIL-10 for HCMV) or manipulation of the cellular IL-10 signaling cascade. Based on the in vitro demonstrations of its pleiotropic and cell type-dependent modulatory nature, hcmvIL-10 could profoundly attenuate host immunity, facilitating the establishment and maintenance of a persistent infection in an immune-competent host. To investigate the impact of extrinsic IL-10 on the induction and maintenance of antiviral immune responses in vivo, rhesus macaques were inoculated with variants of rhesus cytomegalovirus (RhCMV) either expressing or lacking the RhCMV ortholog of hcmvIL-10 (rhcmvIL-10). The results show that rhcmvIL-10 alters the earliest host responses to viral antigens by dampening the magnitude and specificity of innate effector cells to primary RhCMV infection. In addition, there is a commensurate reduction in the quality and quantity of early and long-term, RhCMV-specific adaptive immune responses. These findings provide a mechanistic basis of how early interactions between a newly infected host and HCMV could shape the long-term virus-host balance, which may facilitate the development of new prevention and intervention strategies for HCMV.
authors.affiliation: Center for Comparative Medicine, University of California, Davis, CA 95616, USA.
authors.forename: W L William
authors.initials: WL
authors.lastname: Chang
authors.forename: Peter A
authors.initials: PA
authors.lastname: Barry
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000473:pathology / Q000821:virology; D008297:Male; D008856:Microscopy, Fluorescence; D009154:Mutation; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017077:Culture Media, Conditioned; D016753:Interleukin-10; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D014764:Viral Proteins; D000099192:CD69 Antigens