Open AccessAttenuation of innate immunity by cytomegalovirus IL-10 establishes a long-term deficit of adaptive antiviral immunity
Author(s) -
W. L. William Chang,
Peter A. Barry
Publication year - 2010
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1013794108
Subject(s) - biology , human cytomegalovirus , immune system , cytomegalovirus , immunity , acquired immune system , immunology , innate immune system , virology , virus , effector , herpesviridae , viral disease
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.