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 vectors.

Abstract

Expression from a short human cytomegalovirus (HCMV) major immediate early (IE) promoter-enhancer was tested in three different virus vectors: recombinant adenovirus (Ad), recombinant herpes simplex virus type 1 (HSV-1) and HSV-1-derived amplicon vectors. The HCMV major IE promoter-enhancer within a replication-deficient recombinant Ad vector was shown to produce cell-specific expression in rat nervous system cell cultures. Recombinant Ad entered all cell types examined but the HCMV major IE promoter was silent in primary cultures of neocortical neurons and Schwann cells, although it drove transgene expression in astrocytes 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-competent Ad and HCMV. The HCMV major IE promoter-enhancer was active in neurons when inserted into HSV-1 recombinant vectors. Further experiments 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 inserted into a replication-deficient Ad vector.