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Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22647-52. doi: 10.1073/pnas.1013794108. Epub 2010 Dec 13.

Attenuation of innate immunity by cytomegalovirus IL-10 establishes a long-term deficit of adaptive antiviral immunity.

Author information

1
Center for Comparative Medicine, University of California, Davis, CA 95616, USA.

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.

PMID:
21149711
PMCID:
PMC3012498
DOI:
10.1073/pnas.1013794108
[Indexed for MEDLINE]
Free PMC Article

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