Published online before print November 2, 2004
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*Department of Medicine, Karolinska Systems Biomedicine Center, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical and Experimental Medicine, University of Bologna, Italy; and Abteilung Virologie, Universitätsklinikum Ulm, Germany
@ To whom correspondence should be addressed. E-mail: cecilia.soderberg.naucler{at}cmm.ki.se.
Dendritic cells (DC) play a key role in the host immune response to infections. Human cytomegalovirus (HCMV) infection can inhibit the maturation of DC and impair their ability to stimulate T cell proliferation and cytotoxicity. In this study, we assessed the effects of HCMV infection on the migratory behavior of human DC. The HCMV strain TB40/E inhibited the migration of immature monocyte-derived DC in response to inflammatory chemokines by 95% 1 day after infection. This inhibition was mediated by early viral replicative events, which significantly reduced the cell-surface expression of CC chemokine receptor 1 (CCR1) and CCR5 by receptor internalization. CMV infection also induced secretion of the inflammatory chemokines CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein-1
(MIP-1), CCL4/MIP-1
, and CCL5/regulated on activation, normal T expressed and secreted. Neutralizing antibodies for these chemokines reduced the effects of HCMV on chemokine receptor expression and on DC migration by 
60%. It is interesting that the surface expression of the lymphoid CCR7 was not up-regulated after HCMV infection on immature DC, and immature-infected DC did not migrate in response to CCL19/MIP-3. These findings suggest that blocking the migratory ability of DC may be a potent mechanism used by HCMV to paralyze the early immune response of the host.
Key Words: viral infection • antigen-presenting cells • chemotaxis • chemokines
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