The herpes simplex virus protein Vmw65 can trans-activate both viral and cellular promoters in neuronal cells

Abstract

Transcription of the herpes simplex virus (HSV) immediate-early (IE) genes in lytic infection is dependent upon the formation of a complex between the cellular transcription factor Oct-1 and the HSV virion protein Vmw65. This complex then binds to the TAATGARAT sequence in the IE promoters and trans-activates the IE genes. Following infection of neuronal cells such as the C1300 neuroblastoma cell line, however, the viral (IE) genes are not transcribed and the lytic cycle is aborted at an early stage. We show here that the cellular factors necessary to form a trans-activating complex with Vmw65 are present in C1300 cells and that trans-activation of both viral and cellular promoters by Vmw65 can be observed in these cells. In contrast with permissive cells, however, trans-activation is only observed in C1300 cells at a high concentration of the target viral promoter and not at a low concentration of the target promoter, regardless of the amount of Vmw65 transfected. The significance of these effects for the regulation of latent infection and cellular gene expression in neuronal cells is discussed.