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J. Virol. doi:10.1128/JVI.02197-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Human Cytomegalovirus Down-regulates the Expression of Receptors for Platelet Derived Growth Factor by Smooth Muscle Cells

Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Atherosclerosis Research Unit, King Gustaf V Resesarch Institute, Karolinska Institutet, Stockholm, Sweden

^* To whom correspondence should be addressed. Email: Cecilia.soderberg.naucler{at}ki.se.

	Abstract

Infection by human cytomegalovirus (HCMV) is associated with the development of vascular diseases and may cause severe brain damage in infected fetuses. Platelet-Derived Growth Factor Receptors -alpha and -beta (PDGFR- and -) controls important cellular processes associated with atherosclerosis and fetal development. In the present investigation, our goal was to determine whether infection by HCMV can influence the expression of PDGFR- and - in human smooth muscle cells (SMC).

In connection with HCMV infection in vitro the levels of PDGFR- and - at the cell surface and in the total cellular protein of SMCs were reduced in parallel with decreases in the levels of the corresponding mRNAs. These effects were dependent on immediate early (IE) or early (E) HCMV gene products, since inhibition of late (L) genes, did not prevent HCMV to affect the expression of PDGFR- and -. The down-regulation of PDGFR caused by HCMV was dose-dependent. Furthermore, confocal microscopy revealed that the localization of PDGFR- was altered in HCMV-infected cells, in which this protein co-localized with proteins associated with endosomes (Rab4 and 5) and lysosomes (Lamp1 and 2), indicating entrance into pathways for protein degradation.

Altogether these observations indicate that an IE and/or E HCMV protein(s) down-regulates the expression of PDGFR- and - in SMC. This phenomenon may disrupt cellular processes of importance in connection with cellular differentiation, migration and/or proliferation. These observations may explain why congenital infection with HCMV can cause fetal brain damage.