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Journal of Virology, August 2006, p. 7578-7589, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.02421-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus Subverts the Functions of Monocytes, Impairing Chemokine-Mediated Migration and Leukocyte Recruitment

Giada Frascaroli,1,3 Stefania Varani,3,4 Barbara Moepps,2 Christian Sinzger,5 Maria Paola Landini,3 and Thomas Mertens1*

Institute for Virology,1 Pharmacology and Toxicology, University of Ulm, Ulm, Germany,2 Section of Microbiology, Department of Clinical and Experimental Medicine, University of Bologna, Bologna, Italy,3 Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden,4 Institute for Medical Virology, University of Tübingen, Tübingen, Germany5

Received 17 November 2005/ Accepted 20 April 2006

Despite their role in innate and adaptive immunity, during human cytomegalovirus (HCMV) infection, monocytes are considered to be an important target of infection, a site of latency, and vehicles for virus dissemination. Since chemokine receptors play crucial roles in monocyte activation and trafficking, we investigated the effects of HCMV on their expression and function. By using endotheliotropic strains of HCMV, we obtained high rates (roughly 50%) of in vitro-infected monocytes but only restricted viral gene expression. At 24 h after infection, while the chemokine receptors CX3CR and CCR7 were unaffected, CCR1, CCR2, CCR5, and CXCR4 were downmodulated on the cell surface and retained intracellularly. Structural components of the viral particles, but not viral gene expression or soluble factors released from infected cells, accounted for the changed localization of the receptor molecules and for the block of chemokine-driven migration. HCMV-infected monocytes indeed became unresponsive to inflammatory and homeostatic chemokines, although the basal cell motility and responsiveness to N-formyl-Met-Leu-Phe were unaffected or slightly increased. The production of inflammatory mediators responsible for the recruitment of other immune cells was also hampered by HCMV. Whereas endothelial and fibroblast cells infected by HCMV efficiently recruited leukocytes, infected monocytes were unable to recruit lymphocytes, monocytes, and neutrophils. Our data further highlight the complex level of interference exerted by HCMV on the host immune system.

* Corresponding author. Mailing address: Institute for Virology, University of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm, Germany. Phone: 49 731 5023341. Fax: 49 731 5023337. E-mail: thomas.mertens{at}uniklinik-ulm.de.

Journal of Virology, August 2006, p. 7578-7589, Vol. 80, No. 15
0022-538X/06/$08.00+0     doi:10.1128/JVI.02421-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Frascaroli, G., Varani, S., Blankenhorn, N., Pretsch, R., Bacher, M., Leng, L., Bucala, R., Landini, M. P., Mertens, T. (2009). Human Cytomegalovirus Paralyzes Macrophage Motility through Down-Regulation of Chemokine Receptors, Reorganization of the Cytoskeleton, and Release of Macrophage Migration Inhibitory Factor. J. Immunol. 182: 477-488 [Abstract] [Full Text]  
  • Case, R., Sharp, E., Benned-Jensen, T., Rosenkilde, M. M., Davis-Poynter, N., Farrell, H. E. (2008). Functional Analysis of the Murine Cytomegalovirus Chemokine Receptor Homologue M33: Ablation of Constitutive Signaling Is Associated with an Attenuated Phenotype In Vivo. J. Virol. 82: 1884-1898 [Abstract] [Full Text]  


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