Herpes simplex virus infections are arrested in Oct-1-deficient cells.
Maurício Lacerda Nogueira,Victoria E. H. Wang,Dean Tantin,Phillip A. Sharp,Thomas M. Kristie +4 more
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TLDR
Surprisingly, whereas the viral IE genes are expressed after high moi infection ofOct-1-deficient cells, the assembly of viral replication factories is severely impaired, revealing a second critical role for Oct-1 in HSV replication.Abstract:
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.read more
Citations
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DNA repair proteins affect the lifecycle of herpes simplex virus 1
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The octamer binding transcription factor Oct-1 is a stress sensor
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Control of α-herpesvirus IE gene expression by HCF-1 coupled chromatin modification activities
TL;DR: Studies using model viral promoter-reporter systems as well as analyses of components recruited to the viral genome during the initiation of infection have elucidated the significance of HCF-1 chromatin modification complexes in contributing to the final state of modified histones assembled on the viral IE promoters.
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Joanna Wysocka,Winship Herr +1 more
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