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Journal of Virology, May 2004, p. 4444-4453, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4444-4453.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus Induces Monocyte Differentiation and Migration as a Strategy for Dissemination and Persistence

M. Shane Smith,1,2 Gretchen L. Bentz,1,2 J. Steven Alexander,3 and Andrew D. Yurochko1,2,4*

Department of Microbiology and Immunology,1 Center for Molecular and Tumor Virology,2 Department of Molecular and Cellular Physiology,3 Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-39324

Received 19 August 2003/ Accepted 30 December 2003

Human cytomegalovirus (HCMV) pathogenesis is characterized by multiple organ system involvement due to viral spread to host organs after a cell-associated viremia. The cell type responsible for HCMV dissemination is unknown. Monocytes are the most likely candidate since they are the predominant cell type infected in the blood. However, monocytes are not productive for viral replication and are abortively infected. The results presented here provide a potential answer to this conundrum. We report that primary HCMV infection of monocytes induces transendothelial migration and monocyte-to-macrophage differentiation and that these HCMV-differentiated macrophages are productive for viral replication. Together, our data suggest a novel mechanism for HCMV pathogenesis; HCMV induces cellular changes in monocytes to promote viral replication and spread to host organs.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932. Phone: (318) 675-8332. Fax: (318) 675-5764. E-mail: ayuroc{at}lsuhsc.edu.

Journal of Virology, May 2004, p. 4444-4453, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4444-4453.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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