This Article Full Text (PDF) Other Versions of this Article: JVI.02173-07v1 82/7/3736    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Jenkins, C. Articles by Slobedman, B. Search for Related Content PubMed PubMed Citation Articles by Jenkins, C. Articles by Slobedman, B.

 Previous Article  |  Next Article 

J. Virol. doi:10.1128/JVI.02173-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Immunomodulatory Properties of a Viral Homolog of Human Interleukin-10 Expressed by Human Cytomegalovirus During the Latent Phase of Infection

Centre for Virus Research, Westmead Millennium Institute and University of Sydney, Westmead, New South Wales, 2145, Australia, Department Infectious Diseases and Immunology, University of Sydney, New South Wales, 2006, Australia, University of San Francisco, San Francisco, CA 94117

^* To whom correspondence should be addressed. Email: barry_slobedman{at}wmi.usyd.edu.au.

	Abstract

Human cytomegalovirus (HCMV) establishes a latent infection in haematopoietic cells, from which it can reactivate to cause significant disease in immunocompromised individuals. HCMV expresses a functional homolog of the immunosuppressive cytokine IL-10 (termed cmvIL-10) and alternate splicing of the cmvIL-10 transcript results in expression of a latency associated (LA) cmvIL-10 transcript. To determine whether LAcmvIL-10 encodes immunosuppressive functions, recombinant LAcmvIL-10 protein was generated and its impact on MHC class II expression examined on granulocyte macrophage progenitor cells (GM-Ps) and monocytes. LAcmvIL-10 (and cmvIL-10) downregulated MHC class II on the surfaces of both cell types. This downregulation was associated with a decrease in total MHC class II protein and transcription of components of the MHC class II biosynthesis pathway. Unlike cmvIL-10, LAcmvIL-10 did not trigger phosphorylation of Stat3, and its ability to downregulate MHC class II was not blocked by neutralising antibodies to the human IL-10 receptor, suggesting that LAcmvIL-10 either does not engage the cellular IL-10 receptor, or utilizes it in a different manner to that of cmvIL-10. The impact of LAcmvIL-10 on dendritic cell (DC) maturation was also assessed. In contrast to cmvIL-10, LAcmvIL-10 did not inhibit the expression of co-stimulatory molecules CD40, CD80, CD86 and the maturation marker CD83 on DCs, nor inhibit pro-inflammatory cytokines (IL-1, IL-1, IL-6 and TNF-). Thus, LAcmvIL-10 retains some, but not all, of the immunosuppressive functions of cmvIL-10. As GM-Ps and monocytes support latent infection, expression of LAcmvIL-10 may enable HCMV to avoid immune recognition and clearance during latency.