摘要
The molecular mechanisms mediating herpes simplex virus type 1 （HSV- 1） gene silencing during latent infection are not clear. Five copies of early growth response gene 1 （Egr-1） binding elements were identified in the intron of HSVol ICP22 （infected cell protein No. 22） gene, leading to the hypothesis that Egro 1 binds to the viral genome and regulates the viral gene expression. Transient co-transfection assays indicated that Egr-1 negatively regulated the transcription of both full-length and intron-removed ICP22 promoters. The same assays also revealed that Egr-1 repressed ICP4 （infected cell protein No. 4） promoter activity in a dose-dependent manner but showed less inhibition when the intron was removed. Histone deacetylation was not involved in this regulation since histone deacetylase inhibitor trichostatin A did not exhibit any effect on Egr-l-mediated repression. Chromatin immunoprecipitation assays showed that Egr-1 reduced the binding of Spl to the promoters and that the co-repressor Nab2 （NGFI-A/EGRl-binding protein） was recruited to the proximity of ICP4 in the presence of Egr-1. These results suggested that the multi functional transcription factor Egr-1 can repress HSV-1 immediate-early gene expression through the recruitment ofco-repressor Nab2 and reduction of Sp 1 occupancy, and thus may play a critical role in HSV-1 gene silencing during latency.
