Abstract
ABSTRACTCytomegalovirus (CMV) has highly evolved mechanisms for avoiding detection by the host immune system. Recently, in the genomes of human and primate CMV, a novel gene comprising segments of noncontiguous open reading frames was identified and found to have limited predicted homology to endogenous cellular interleukin-10 (IL-10). Here we investigate the biological activities of the CMV IL-10-like gene product and show it to possess potent immunosuppressive properties. Both purified bacterium-derived recombinant CMV IL-10 and CMV IL-10 expressed in supernatants of human cells were found to inhibit proliferation of mitogen-stimulated peripheral blood mononuclear cells (PBMCs), with specific activity comparable to that of recombinant human IL-10. In addition, CMV IL-10 expressed from human cells inhibited cytokine synthesis, as treatment of stimulated PBMCs and monocytes with CMV IL-10 led to a marked decrease in production of proinflammatory cytokines. Finally, CMV IL-10 was observed to decrease cell surface expression of both major histocompatibility complex (MHC) class I and class II molecules, while conversely increasing expression of the nonclassical MHC allele HLA-G. These results demonstrate for the first time that CMV has a biologically active IL-10 homolog that may contribute to immune evasion during virus infection.
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Dates
Type | When |
---|---|
Created | 14 years, 9 months ago (Oct. 27, 2010, 10:32 a.m.) |
Deposited | 2 years, 2 months ago (June 3, 2023, 9:29 p.m.) |
Indexed | 4 days, 19 hours ago (Aug. 19, 2025, 5:58 a.m.) |
Issued | 23 years, 6 months ago (Feb. 1, 2002) |
Published | 23 years, 6 months ago (Feb. 1, 2002) |
Published Print | 23 years, 6 months ago (Feb. 1, 2002) |
@article{Spencer_2002, title={Potent Immunosuppressive Activities of Cytomegalovirus- Encoded Interleukin-10}, volume={76}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.76.3.1285-1292.2002}, DOI={10.1128/jvi.76.3.1285-1292.2002}, number={3}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Spencer, Juliet V. and Lockridge, Kristen M. and Barry, Peter A. and Lin, Gaofeng and Tsang, Monica and Penfold, Mark E. T. and Schall, Thomas J.}, year={2002}, month=feb, pages={1285–1292} }