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Journal of Virology, February 2003, p. 2182-2194, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.2182-2194.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Cytomegalovirus-Mediated Upregulation of Chemokine Expression Correlates with the Acceleration of Chronic Rejection in Rat Heart Transplants

Daniel N. Streblow,1 Craig Kreklywich,1,2 Qiang Yin,2,3 V. T. De La Melena,2 Christopher L. Corless,3,4 Patricia A. Smith,1 Christina Brakebill,2 Judith W. Cook,2 Cornelis Vink,5 Cathrien A. Bruggeman,5 Jay A. Nelson,1,6 and Susan L. Orloff1,2,3*

Departments of Molecular Microbiology,1 Surgery,2 and Pathology,4 and The Gene Therapy Institute,6 Oregon Health Sciences University, and Portland Veterans Affairs Medical Center, Portland, Oregon 97201,3 and Department of Microbiology, University of Maastricht, Maastricht, The Netherlands5

Received 19 July 2002/ Accepted 28 October 2002

Cytomegalovirus (CMV) infections have been shown to dramatically affect solid organ transplant graft survival in both human and animal models. Recently, it was demonstrated that rat CMV (RCMV) infection accelerates the development of transplant vascular sclerosis (TVS) in both rat heart and small bowel graft transplants. However, the mechanisms involved in this process are still unclear. In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat heart transplant model. Acute RCMV infection enhances the development of TVS in rat heart allografts, and this process is initiated between 21 and 24 days posttransplantation. The virus is consistently detected in the heart grafts from day 7 until day 35 posttransplantation but is rarely found at the time of graft rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had upregulation of chemokine expression compared to uninfected controls, and the timing of this increased expression paralleled that of RCMV-accelerated neointimal formation. In addition, graft vessels from RCMV-infected grafts demonstrate the increased infiltration of T cells and macrophages during periods of highest chemokine expression. These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression.

* Corresponding author. Mailing address: Department of Surgery, mc L590, 3181 SW Sam Jackson Park Rd., Portland, OR 97201. Phone: (503) 494-7810. Fax: (503) 494-5292. E-mail: orloffs{at}ohsu.edu.

Journal of Virology, February 2003, p. 2182-2194, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.2182-2194.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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