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Journal of Virology, January 2009, p. 830-835, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01363-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Infection with Human Cytomegalovirus Alters the MMP-9/TIMP-1 Balance in Human Macrophages{triangledown}

Klas Strååt,1 Rainier de Klark,1 Sara Gredmark-Russ,1,{dagger} Per Eriksson,2,{ddagger} and Cecilia Söderberg-Nauclér1,{ddagger}*

Experimental Cardiovascular Research Unit,1 Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden2

Received 30 June 2008/ Accepted 14 October 2008

Human cytomegalovirus (HCMV) has been suggested to contribute to the development of vascular diseases. Since matrix metalloproteinases (MMPs) have been implicated in atherosclerosis and plaque rupture, we investigated the effect of HCMV infection on MMP expression in human macrophages. We used quantitative real-time PCR, Western blotting, and gelatin zymography to study the expression and activity of MMP-2, -3, -7, -9, -12, -13, and -14 and of tissue inhibitor of metalloproteinase 1 (TIMP-1), -2, -3, and -4. HCMV infection reduced MMP-9 mRNA, protein, and activity levels but increased TIMP-1 mRNA and protein levels. Furthermore, a decrease in MMP-12, MMP-14, TIMP-2, and TIMP-3 mRNA levels could be detected. The MMP-9 and TIMP-1 mRNA alterations required viral replication. MMP-9 mRNA expression was affected by an immediate-early or early viral gene product, whereas TIMP-1 mRNA expression was affected by late viral gene products. We conclude that HCMV infection specifically alters the MMP-9/TIMP-1 balance in human macrophages, which in turn reduces MMP-9 activity in infected cells. Since MMP-9 prevents atherosclerotic plaque development in mice, these results suggest that HCMV may contribute to atherogenesis through specific effects on MMP-9 activity.

* Corresponding author. Mailing address: Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden. Phone: 46851779844. Fax: 468313147. E-mail: Cecilia.naucler{at}ki.se

{triangledown} Published ahead of print on 22 October 2008.

{dagger} Present address: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142.

{ddagger} Shared senior authorship.

Journal of Virology, January 2009, p. 830-835, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01363-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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