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

TitleTranscriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency.
Publication TypeJournal Article
Year of Publication2017
AuthorsAlfonso-Dunn, R, Turner, A-MW, Beltran, PMJean, Arbuckle, JH, Budayeva, HG, Cristea, IM, Kristie, TM
JournalCell Host Microbe
Volume21
Issue4
Pagination507-517.e5
Date Published2017 Apr 12
ISSN1934-6069
KeywordsAnimals, Cell Line, Epithelial Cells, Ganglia, Sensory, Gene Expression Regulation, Viral, Genes, Immediate-Early, Host Cell Factor C1, Humans, Mice, Simplexvirus, Transcription Elongation, Genetic, Transcription Factors, Virus Activation
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.

DOI10.1016/j.chom.2017.03.007
Alternate JournalCell Host Microbe
PubMed ID28407486
Grant ListR01 GM114141 / GM / NIGMS NIH HHS / United States