Cytomegalovirus infection, viral DNA, and immediate early-1 gene expression in rejecting rat liver allografts.
BACKGROUND
Cytomegalovirus (CMV) infection has been linked to acute and chronic rejection. We have previously shown that concomitant rat cytomegalovirus (RCMV) infection increases portal inflammation and bile duct destruction in rejecting rat liver allografts. Many of the pro-inflammatory effects of CMV have been attributed to the immediate early (IE) proteins of CMV. We wanted to investigate whether RCMV and IE-1 gene expression persist in the liver graft in our model.


METHODS
Liver transplantations were performed from PVG (RT1c) into BN (RT1n) rats. One day after transplantation, the rats were infected with RCMV. No immunosuppression was given. The graft infection was studied by viral culture, immunofluorescence, DNA in situ hybridization and RT-PCR for the detection of IE-1 mRNA at various time points.


RESULTS
RCMV caused an active infection from 5 days to 2 weeks after transplantation, during which infectious virus was found in the graft. Thereafter the cultures were negative. RCMV antigens and DNA were found in hepatocytes, endothelial, inflammatory, and bile duct cells during the active infection. At 4 weeks, RCMV DNA positive hepatocytes, endothelial, inflamma tory, and bile duct cells could still be found, but in much smaller quantities. IE-1 mRNA expression was, however, only detected during the active infection, not at 4 weeks postinfection.


CONCLUSIONS
RCMV IE-1 expression does not persist in the graft after the active infection, although some viral DNA can be detected in the graft up to 4 weeks. In our model, the CMV-induced increase in graft damage does not seem to require the continued expression of IE-1.
Martelius
T J
TJ
Department of Surgery, Helsinki University Hospital, Finland.
Blok
M J
MJ
Inkinen
K A
KA
Loginov
R J
RJ
Höckerstedt
K A
KA
Bruggeman
C A
CA
Lautenschlager
I T
IT
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000378:metabolism*; D015870:Gene Expression; D017781:Genes, Immediate-Early / Q000235:genetics*; D005814:Genes, Viral / Q000235:genetics*; D006084:Graft Rejection / Q000235:genetics / Q000821:virology; D017403:In Situ Hybridization; D016031:Liver Transplantation / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN
D000956:Antigens, Viral; D004279:DNA, Viral; D012333:RNA, Messenger