Transcription factor USF, expressed during the entire phase of varicella-zoster virus infection, interacts physically with the major viral transactivator IE62 and plays a significant role in virus replication.

The expression of the genes of varicella-zoster virus (VZV) is regulated by self-encoded viral as well as cellular transcription factors. A potential candidate with an ability to influence the transcription of VZV genes is USF (upstream stimulatory factor), which recognizes the consensus E-box motif. Quantitative RT-PCR and immunoblot assays indicate stable expression of both USF1 and USF2 throughout infection. It was also found that USF binds to a variety of E-boxes (consensus and closely related motifs) within the promoters of ORF 8/9 (two elements), ORF 22 and ORF 67. Co-immunoprecipitation experiments and His-tag protein affinity pull-down assays indicate that a direct physical interaction occurs between USF and the major virus transactivator IE62. To study the general effects of USF in the replication of VZV, a cell line expressing a dominant-negative form of USF (A-USF), which inhibits binding of USF to its recognition sites, was created. A significant decrease in virus replication was detected when this cell line was infected with cell-free virus, indicating that USF is an important cellular factor that regulates the transcription of VZV genes.