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.
Rahaus
Markus
M
Institute of Microbiology and Virology, University of Witten/Herdecke, Stockumer Str. 10, D-58448 Witten, Germany.
Desloges
Nathalie
N
Institute of Microbiology and Virology, University of Witten/Herdecke, Stockumer Str. 10, D-58448 Witten, Germany.
Yang
Min
M
Department of Microbiology, State University of New York at Buffalo, 138 Farber Hall, Buffalo, NY 14214, USA.
Ruyechan
William T
WT
Department of Microbiology, State University of New York at Buffalo, 138 Farber Hall, Buffalo, NY 14214, USA.
Wolff
Manfred H
MH
Institute of Microbiology and Virology, University of Witten/Herdecke, Stockumer Str. 10, D-58448 Witten, Germany.
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051720:Upstream Stimulatory Factors; D014759:Viral Envelope Proteins / Q000502:physiology*; D014779:Virus Replication
D004268:DNA-Binding Proteins; C074221:IE62 protein, Human herpesvirus 3; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D014759:Viral Envelope Proteins; D004247:DNA