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Journal of Virology, December 2002, p. 12803-12812, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12803-12812.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Upregulation of CD40 Expression on Endothelial Cells Infected with Human Cytomegalovirus

Tim Maisch,1 Barbara Kropff,1 Christian Sinzger,2 and Michael Mach1*

Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, 91054 Erlangen,1 Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten, Universität Tübingen, 72076 Tübingen, Germany2

Received 28 May 2002/ Accepted 4 September 2002

CD40 has been identified as an important molecule for a number of processes, such as immune responses, inflammation, and the activation of endothelia. We investigated CD40 in endothelial cells (EC) following infection with an endotheliotropic strain of human cytomegalovirus (HCMV). Between 8 and 72 h postinfection, we observed a significant increase in CD40 levels on the surface of infected EC, as measured by fluorescence-activated cell sorting analysis. As a consequence of CD40 upregulation, increased levels of E-selectin were found on infected EC after stimulation with CD154-expressing T cells. Enhanced expression of CD40 was specific for EC, since infection of fibroblasts did not result in the upregulation of CD40. The addition of neutralizing antibodies as well as UV inactivation of virus completely prevented the upregulation of CD40 on EC. Also, laboratory-adapted HCMV strain AD169 was not able to induce CD40 on EC. De novo protein synthesis was necessary for the increased surface expression. At early times (4 to 24 h) postinfection, this change was not accompanied by increased levels of CD40 protein or mRNA. At late times (48 to 96 h) postinfection, increased amounts of CD40 protein and mRNA were detected. Immunohistochemical analysis of infected tissues demonstrated elevated levels of CD40 on HCMV-infected EC in vivo. Thus, infection of EC by HCMV may result in the activation of endothelia and in the augmentation of inflammatory processes.

* Corresponding author. Mailing address: Institut für Klinische und Molekulare Virologie, Schlossgarten 4, 91054 Erlangen, Germany. Phone: 49 9131 8522107. Fax: 49 9131 8522101. E-mail: mlmach{at}viro.med.uni-erlangen.de.

Journal of Virology, December 2002, p. 12803-12812, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12803-12812.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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