HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stern, J. L. Articles by Slobedman, B. Search for Related Content PubMed PubMed Citation Articles by Stern, J. L. Articles by Slobedman, B.

Human Cytomegalovirus Latent Infection of Myeloid Cells Directs Monocyte Migration by Up-Regulating Monocyte Chemotactic Protein-1¹

Centre for Virus Research, Westmead Millennium Institute and the University of Sydney, Westmead, New South Wales, Australia

Following primary infection, human cytomegalovirus (HCMV) establishes a latent infection in hematopoietic cells from which it reactivates to cause serious disease in immunosuppressed patients such as allograft recipients. HCMV is a common cause of disease in newborns and transplant patients and has also been linked with vascular diseases such as primary and post-transplant arteriosclerosis. A major factor in the pathogenesis of vascular disease is the CC chemokine MCP-1. In this study, we demonstrate that granulocyte macrophage progenitors (GMPs) latently infected with HCMV significantly increased expression of MCP-1 and that this phenotype was dependent on infection with viable virus. Inhibitors of a subset of G proteins and PI3K inhibited the up-regulation of MCP-1 in latently infected cultures, suggesting that the mechanism underlying this phenotype involves signaling through a G-protein coupled receptor. In GMPs infected with the low passage viral strain Toledo, up-regulated MCP-1 was restricted to a subset of myeloid progenitor cells expressing CD33, HLA-DR, and CD14 but not CD1a, CD15, or CD16, and the increase in MCP-1 was sufficient to enhance migration of CD14⁺ monocytes to latently infected cells. Latent HCMV-mediated up-regulation of MCP-1 provides a mechanism by which HCMV may contribute to vascular disease during the latent phase of infection or facilitate dissemination of virus upon reactivation from latency.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Australian National Health and Medical Research Council Grants 301943, 301942, and 358399.

² Address correspondence and reprint requests to Dr. Barry Slobedman, Centre for Virus Research, Westmead Millennium Institute, PO Box 412, Westmead New South Wales 2145, Australia. E-mail address: barry_slobedman{at}wmi.usyd.edu.au

³ Abbreviations used in this paper: HCMV, human cytomegalovirus; DC, dendritic cell; MCMV, murine CMV; rhMCP-1, recombinant human MCP-1; gB, glycoprotein B; RTK, receptor tyrosine kinase; GPCR, G-protein coupled receptor; HFF, human foreskin fibroblast; GMP, granulocyte macrophage progenitor.