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Journal of Virology, July 2008, p. 6524-6535, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00502-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing{triangledown}

Jerome Dumortier,4 Daniel N. Streblow,4 Ashlee V. Moses,4 Jon M. Jacobs,5 Craig N. Kreklywich,2 David Camp,5 Richard D. Smith,5 Susan L. Orloff,1,2,3 and Jay A. Nelson2,4*

Veterans Affairs, Portland VAMC, Portland, Oregon,1 MMI,2 Department of Surgery, Oregon Health Sciences University, Portland, Oregon,3 Vaccine and Gene Therapy Institute, Oregon Health Sciences University, Portland, Oregon,4 Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington 993525

Received 6 March 2008/ Accepted 21 April 2008

Human cytomegalovirus (HCMV) is implicated in the acceleration of a number of vascular diseases including transplant vascular sclerosis (TVS), the lesion associated with chronic rejection (CR) of solid organ transplants. Although the virus persists in the allograft throughout the course of disease, few cells are directly infected by CMV. This observation is in contrast to the global effects that CMV has on the acceleration of TVS/CR, suggesting that CMV infection indirectly promotes the vascular disease process. Recent transcriptome analysis of CMV-infected heart allografts indicates that the virus induces cytokines and growth factors associated with angiogenesis (AG) and wound healing (WH), suggesting that CMV may accelerate TVS/CR through the induction and secretion of AG/WH factors from infected cells. We analyzed virus-free supernatants from HCMV-infected cells (HCMV secretomes) for growth factors, by mass spectrometry and immunoassays, and found that the HCMV secretome contains over 1,000 cellular proteins, many of which are involved in AG/WH. Importantly, functional assays demonstrated that CMV but not herpes simplex virus secretomes not only induce AG/WH but also promote neovessel stabilization and endothelial cell survival for 2 weeks. These findings suggest that CMV acceleration of TVS occurs through virus-induced growth factors and cytokines in the CMV secretome.

* Corresponding author. Mailing address: Oregon Health Sciences University, Vaccine and Gene Therapy Institute, Mail Code VGTI, 505 N.W. 185th Ave., Beaverton, OR 97006-3499. Phone: (503) 494-7769. Fax: (503) 494-2441. E-mail: nelsonj{at}ohsu.edu

{triangledown} Published ahead of print on 30 April 2008.

Journal of Virology, July 2008, p. 6524-6535, Vol. 82, No. 13
0022-538X/08/$08.00+0     doi:10.1128/JVI.00502-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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