DEVELOPMENTAL ANALYSIS OF THE CYTOMEGALOVIRUS ENHANCER IN TRANSGENIC ANIMALS

The major immediate-early promoter (MIEP) of human cytomegalovirus (HC MV) constitutes a primary genetic switch for viral activation. In this study, regulation of the enhancer-containing segment (nucleotides -67 0 to +54) of the HCMV MIEP attached to the lacZ reporter gene was exam ined in the developing embryos of transgenic mice to identify temporal and tissue-specific expression. We find that the transgene reporter i s first detected as a dorsal stripe of expression in the neural folds of embryos at day 8.5 postcoitum (p.c.). A broad expression pattern is exhibited in embryos at day 9.5 p.c. This pattern becomes more restri cted by day 10.5 p.c. as organogenesis progresses. By day 14.5 p.c., p rominent expression is observed in a subpopulation of central nervous system cells and spinal ganglia, endothelial cells, muscle, shin, thyr oid, parathyroid, kidney, lung, liver, and gut cells, and the pancreas and submandibular and pituitary glands. This distribution pattern is discussed in relation to human congenital HCMV infection. These result s suggest that the transcriptional activity of the HCMV MIEP may deter mine in part, the ability of the virus to specifically target developi ng fetal tissues in utero.