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Journal of Virology, May 2001, p. 4814-4822, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4814-4822.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Allogeneic Transplantation Induces Expression of Cytomegalovirus Immediate-Early Genes In Vivo: a Model for Reactivation from Latency

Mary Hummel,1,2 Zheng Zhang,1 Shixian Yan,1 Isabelle DePlaen,3 Piyush Golia,1 Thomas Varghese,1 Gail Thomas,1 and Michael I. Abecassis1,*

Department of Surgery, Division of Organ Transplantation,1 Department of Microbiology and Immunology,2 and Department of Pediatrics,3 Northwestern University Medical School, Chicago, Illinois 60611

Received 20 November 2000/Accepted 14 February 2001

Reactivation of cytomegalovirus (CMV) from latency is a frequent complication of organ transplantation, and the molecular mechanism by which this occurs is unknown. Previous studies have shown that allogeneic stimulation induces reactivation of human CMV (HCMV) in vitro (64). We find that transplantation of vascularized allogeneic kidneys induces murine CMV (MCMV) and HCMV immediate-early (ie) gene expression. This induction is accompanied by increased expression of transcripts encoding inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-2, and gamma interferon, and by activation of NF-kappa B. TNF alone can substitute for allogeneic transplantation in inducing HCMV and MCMV ie gene expression in some tissues. Our studies suggest that reactivation is a multistep process which is initiated by factors that induce ie gene expression, including TNF and NF-kappa B. Allogeneic transplantation combined with immunosuppression may be required to achieve complete reactivation in vivo.

* Corresponding author. Mailing address: Division of Organ Transplantation, Northwestern Memorial Hospital, 675 N. St. Clair St., Galter Pavilion, Suite 17-200, Chicago, IL 60611. Phone: (312) 695-8900. Fax: (312) 695-9194. E-mail: mabecass{at}nmh.org.

Journal of Virology, May 2001, p. 4814-4822, Vol. 75, No. 10
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.10.4814-4822.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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