Cytomegalovirus immediate early genes prevent the inhibitory effect of cyclosporin A on interleukin 2 gene transcription.
The use of cyclosporin A (CsA) as an immunosuppressive agent has markedly improved the clinical outcome in solid organ transplantation. However, posttransplantation infection remains a significant problem and may contribute to subsequent organ rejection. In this study the effect of cytomegalovirus (CMV) immediate early (IE) gene products on interleukin 2 (IL-2) gene transcription in the absence and presence of CsA was investigated using a transient transfection system. Jurkat T cells were transfected with plasmids expressing the CMV IE gene products or with a control plasmid. The presence of the CMV IE2 gene product abolished the inhibitory effect of CsA on IL-2 promoter activation and gene transcription. This effect was noted regardless of the time of CsA addition relative to the time of stimulation and was independent of CsA concentration. CsA had no effect on the CMV or the IL-2 receptor promoters. These studies suggest that the CMV IE gene products may play a role in graft rejection after solid organ transplantation.
Geist
L J
LJ
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Monick
M M
MM
Stinski
M F
MF
Hunninghake
G W
GW
D016572:Cyclosporine / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000633:toxicity*; D007376:Interleukin-2 / Q000235:genetics*; D008562:Membrane Glycoproteins; D011401:Promoter Regions, Genetic; D015534:Trans-Activators; D014158:Transcription, Genetic / Q000187:drug effects*; D014759:Viral Envelope Proteins; D014764:Viral Proteins
C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D015534:Trans-Activators; C077406:UL115 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus; D016572:Cyclosporine