Regulation of herpes simplex virus type 1 gene expression in nonpermissive murine resident peritoneal macrophages

The restriction of herpes simplex virus type 1 (HSV-1) gene expression in nonpermissive murine resident peritoneal macrophages (ResPMO) was analyzed at the level of transcription. Using nuclear run-on assays, we established that transcription of a representative gene from each HSV-1 kinetic class was initiated in both ResPMO and permissive Vero cells. Using transient expression assays, we observed that the promoters of two early genes were activated by the immediate-early protein ICP4 in ResPMO. However, the level of transactivation of these promoters by another immediate-early protein, ICP0, was markedly reduced in ResPMO. Furthermore, the synergistic trans-activation normally observed between ICPs 4 and 0 in Vero cells was noticeably absent in ResPMO. The data indicate that the block in viral gene expression in ResPMO occurs after initiation of viral gene transcription and involves dysfunction of a viral immediate-early regulatory protein, ICP0.