Herpes simplex virus infections are arrested in Oct-1-deficient cells.
Expression of the herpes simplex virus (HSV) immediate early (IE) genes is regulated by a multiprotein complex that is assembled on the TAATGARAT enhancer core element. The complex contains the cellular POU domain protein Oct-1, the viral transactivator VP16, and the cellular cofactor host cell factor 1. The current model suggests that the assembly depends on recognition of the core element by Oct-1. Here, HSV infection of Oct-1-deficient mouse embryonic fibroblast cells demonstrates that Oct-1 is critical for IE gene expression at low multiplicities of infection (moi). However, the protein is not essential for IE gene expression at high moi, indicating that VP16-mediated transcriptional induction through other IE regulatory elements is also important. This induction depends, at least in part, on the GA-binding protein binding elements that are present in each IE enhancer domain. Surprisingly, whereas the viral IE genes are expressed after high moi infection of Oct-1-deficient cells, the assembly of viral replication factories is severely impaired, revealing a second critical role for Oct-1 in HSV replication. The results have implications for both the HSV lytic and latency-reactivation cycles.
Nogueira
Mauricio L
ML
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4-131, 4 Center Drive, Bethesda, MD 20892, USA.
Wang
Victoria E H
VE
Tantin
Dean
D
Sharp
Phillip A
PA
Kristie
Thomas M
TM
D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D017781:Genes, Immediate-Early; D006561:Herpes Simplex / Q000235:genetics*; D051863:Host Cell Factor C1; D051379:Mice; D050811:Octamer Transcription Factor-1; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C497693:Hcfc1 protein, mouse; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C494166:Pou2f1 protein, mouse; D014157:Transcription Factors