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Journal of Virology, February 2002, p. 1285-1292, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.1285-1292.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Potent Immunosuppressive Activities of Cytomegalovirus- Encoded Interleukin-10

Juliet V. Spencer,1 Kristen M. Lockridge,2 Peter A. Barry,2 Gaofeng Lin,3 Monica Tsang,3 Mark E. T. Penfold,1 and Thomas J. Schall1*

ChemoCentryx, San Carlos, California 94070,1 Center for Comparative Medicine, University of California at Davis, Davis, California 95616,2 R&D Systems, Minneapolis, Minnesota 554133

Received 18 September 2001/ Accepted 18 October 2001

Cytomegalovirus (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.

* Corresponding author. Mailing address: ChemoCentryx, 1539 Industrial Rd., San Carlos, CA 94070. Phone: (650) 632-2902. Fax: (650) 632-2910. E-mail: tschall{at}chemocentryx.com.

{dagger} Present address: Ceretek, LLC, Alameda, CA 94502.

Journal of Virology, February 2002, p. 1285-1292, Vol. 76, No. 3
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.3.1285-1292.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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