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Journal of Virology, September 2004, p. 10023-10033, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.10023-10033.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus UL131-128 Genes Are Indispensable for Virus Growth in Endothelial Cells and Virus Transfer to Leukocytes

Gabriele Hahn,1* Maria Grazia Revello,2 Marco Patrone,3 Elena Percivalle,2 Giulia Campanini,2 Antonella Sarasini,2 Markus Wagner,1 Andrea Gallina,3 Gabriele Milanesi,3 Ulrich Koszinowski,1 Fausto Baldanti,2 and Giuseppe Gerna2*

Max von Pettenkofer Institut, Abteilung Virologie, Ludwig-Maximilians-Universität München, Munich, Germany,1 Servizio di Virologia, IRCCS Policlinico San Matteo, Pavia,2 Dipartimento di Medicina e Chirurgia, Polo San Paolo, Università degli Studi di Milano, Milan, Italy3

Received 14 November 2003/ Accepted 3 May 2004

Human cytomegalovirus (HCMV), a ubiquitous human pathogen, is the leading cause of birth defects and morbidity in immunocompromised patients and a potential trigger for vascular disease. HCMV replicates in vascular endothelial cells and drives leukocyte-mediated viral dissemination through close endothelium- leukocyte interaction. However, the genetic basis of HCMV growth in endothelial cells and transfer to leukocytes is unknown. We show here that the UL131-128 gene locus of HCMV is indispensable for both productive infection of endothelial cells and transmission to leukocytes. The experimental evidence for this is based on both the loss-of-function phenotype in knockout mutants and natural variants and the gain-of-function phenotype by trans-complementation with individual UL131, UL130, and UL128 genes. Our findings suggest that a common mechanism of virus transfer may be involved in both endothelial cell tropism and leukocyte transfer and shed light on a crucial step in the pathogenesis of HCMV infection.

* Corresponding author. Mailing address for G. Gerna: Servizio di Virologia, IRCCS Policlinico San Matteo, I-27100 Pavia, Italy. Phone: 39-0382-502644. Fax: 39-0382-502599. E-mail: g.gerna{at}smatteo.pv.it. Mailing address for G. Hahn: Max von Pettenkofer Institut, Ludwig-Maximilians-Universität, Pettenkoferstr. 9A, 80336 Munich, Germany. Phone: 49-89-5160-5270. Fax: 49-89-5160-5292. E-mail: ghahn{at}m3401.mpk.med.uni-muenchen.de.

Journal of Virology, September 2004, p. 10023-10033, Vol. 78, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.18.10023-10033.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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