Tissue and cell-specific transcriptional activity of the human cytomegalovirus immediate early gene promoter (UL123) in zebrafish

Abstract

The human cytomegalovirus (CMV) is a member of the herpesvirus superfamily and causes different diseases including encephalitis, gastrointestinal diseases, pneumonitis, hepatitis, and retinitis. The immediate early (IE) gene of the human cytomegalovirus is essential to the viral replication. The proximal promoter region of this gene behaves as a strong enhancer and was commonly used to overexpress genes in vitro and in vivo in numerous cell types and species. However, there was no detailed report on the spatial and temporal transcriptional activity of the human CMV-IE gene promoter in zebrafish. In the present study, we generated stable transgenic zebrafish lines carrying the eGFP reporter gene under the control of the human CMV-IE gene promoter (-602/-14). We demonstrated that the hCMV-IE:eGFP transgene was expressed in numerous tissues but transgene expression was either regionalized or restricted to specific cell types as embryo and larval development progressed. In adult, the global expression pattern was similar but not identical to that described for the simian CMV-IE gene promoter in stable zebrafish with high transgene expression in the spinal cord, olfactory organs, central nervous system, neuromasts, retina, and skeletal muscles. However, we describe additional major expression sites in the hepatocytes, the epithelial cells of the intestine, the epithelial cells of the renal tubules, and the oocytes. Interestingly, our study shows that the tissue and cell specific expression pattern of the human CMV-IE gene promoter is rather well conserved in stable transgenic zebrafish compared to that observed in mouse. The major expression sites described in zebrafish are in agreement with the targeted cells and symptoms resulting from CMV infections in human. Finally, the hCMV:eGFP transgenic lines described in the present study will be valuable tools to trace specific cell lineages in adult zebrafish.