Title | Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Alfonso-Dunn, R, Turner, A-MW, Beltran, PMJean, Arbuckle, JH, Budayeva, HG, Cristea, IM, Kristie, TM |
Journal | Cell Host Microbe |
Volume | 21 |
Issue | 4 |
Pagination | 507-517.e5 |
Date Published | 2017 Apr 12 |
ISSN | 1934-6069 |
Keywords | Animals, 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 | <p>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.</p> |
DOI | 10.1016/j.chom.2017.03.007 |
Alternate Journal | Cell Host Microbe |
PubMed ID | 28407486 |
PubMed Central ID | PMC5997188 |
Grant List | R01 GM114141 / GM / NIGMS NIH HHS / United States |