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Cell Host Microbe. 2017 Apr 12;21(4):507-517.e5. doi: 10.1016/j.chom.2017.03.007.

Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency.

Author information

1
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20814, USA.
2
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
3
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20814, USA. Electronic address: tkristie@niaid.nih.gov.

Abstract

The cellular transcriptional coactivator HCF-1 is required for initiation of herpes simplex virus (HSV) lytic infection and for reactivation from latency in sensory neurons. HCF-1 stabilizes the viral Immediate Early (IE) gene enhancer complex and mediates chromatin transitions to promote IE transcription initiation. In infected cells, HCF-1 was also found to be associated with a network of transcription elongation components including the super elongation complex (SEC). IE genes exhibit characteristics of genes controlled by transcriptional elongation, and the SEC-P-TEFb complex is specifically required to drive the levels of productive IE mRNAs. Significantly, compounds that enhance the levels of SEC-P-TEFb also potently stimulated HSV reactivation from latency both in a sensory ganglia model system and in vivo. Thus, transcriptional elongation of HSV IE genes is a key limiting parameter governing both the initiation of HSV infection and reactivation of latent genomes.

KEYWORDS:

P-TEFb; herpes simplex virus; host cell factor-1; latency; super elongation complex; transcriptional elongation

PMID:
28407486
PMCID:
PMC5997188
DOI:
10.1016/j.chom.2017.03.007
[Indexed for MEDLINE]
Free PMC Article

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