CELL-TYPE-SPECIFIC EXPRESSION IN BRAIN-CELL CULTURES FROM A SHORT HUMAN CYTOMEGALOVIRUS MAJOR IMMEDIATE-EARLY PROMOTER DEPENDS ON WHETHER IT IS INSERTED INTO HERPESVIRUS OR ADENOVIRUS VECTOR

Expression from a short human cytomegalovirus (HCMV) major immediate e arly (IE) promoter-enhancer was tested in three different virus vector s: recombinant adenovirus (Ad), recombinant herpes simplex virus type 1 (HSV-1) and HSV-1-derived amplicon vectors. The HCMV major IE promot er-enhancer within a replication-deficient recombinant Ad vector was s hown to produce cell-specific expression in rat nervous system cell cu ltures. Recombinant Ad entered all cell types examined but the HCMV ma jor IE promoter was silent in primary cultures of neocortical neurons and Schwann cells, although it drove transgene expression in astrocyte s and fibroblasts. Moreover, in neurons and Schwann cells, expression from the HCMV major IE promoter-enhancer in the replication-deficient Ad vector was activated by superinfection with HSV-1, replication-comp etent Ad and HCMV. The HCMV major IE promoter-enhancer was active in n eurons when inserted into HSV-1 recombinant vectors. Further experimen ts with HSV-1-derived amplicons strongly suggested that an IE protein was responsible for the activation of HCMV major IE-induced expression in neurons, This demonstrates that the activity of the HCMV major IE promoter-enhancer element can depend on the expression of other genes encoded in the virus vector backbone within which it is inserted, and that it can function in a neuronal cell type-specific manner when inse rted into a replication-deficient Ad vector.