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Journal of Virology, October 2004, p. 10378-10389, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10378-10389.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus Inhibits Cytokine-Induced Macrophage Differentiation

Sara Gredmark, Tamara Tilburgs, and Cecilia Söderberg-Nauclér*

Karolinska Systems Biomedicine Center, Department of Medicine, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden

Received 20 August 2003/ Accepted 24 May 2004

Human cytomegalovirus (HCMV) infection in immunocompromised patients is associated with impaired immunological function. Blood monocytes, which differentiate into macrophage effector cells, are of central importance for immune reactivity. Here, we demonstrate that HCMV transiently blocks cytokine-induced differentiation of monocytes into functionally active phagocytic macrophages. In HCMV-treated cultures, the cells had classical macrophage markers but lacked the classical morphological appearance of macrophages and had impairments in migration and phagocytosis. Even at very low multiplicities of infection, macrophage differentiation was almost completely inhibited. The inhibition appeared to be mediated by a soluble factor released upon viral treatment of monocytes. Human immunodeficiency virus or measles virus had no such effects. These findings suggest that HCMV impairs immune function by blocking certain aspects of cytokine-induced differentiation of monocytes and demonstrate an efficient pathway for this virus to evade immune recognition that may have clinical implications for the generalized immunosuppression often observed in HCMV-infected patients.

* Corresponding author. Mailing address: Karolinska Institute, Department of Medicine, Center for Molecular Medicine, L8:03, Karolinska Hospital, S-171 76 Stockholm, Sweden. Phone: 46-8-51779896. Fax: 46-8-313147. E-mail: cecilia.soderberg.naucler{at}cmm.ki.se.

Journal of Virology, October 2004, p. 10378-10389, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10378-10389.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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Copyright © 2004 by the American Society for Microbiology. All rights reserved.