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

Publication date: 12 April 2017
Source:Cell Host & Microbe, Volume 21, Issue 4
Author(s): Roberto Alfonso-Dunn, Anne-Marie W. Turner, Pierre M. Jean Beltran, Jesse H. Arbuckle, Hanna G. Budayeva, Ileana M. Cristea, Thomas M. Kristie
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.

Graphical abstract

Teaser

HSV Immediate Early (IE) gene transcription requires the cellular coactivator HCF-1. Alfonso-Dunn et al. demonstrate that during infection, HCF-1 is associated with transcription initiation and elongation components. Both lytic infection and reactivation of latent virus are dependent on elongation factors that mediate a critical checkpoint in viral IE expression.


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