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

Roberto Alfonso-Dunn, Anne Marie W. Turner, Pierre M. Jean Beltran, Jesse H. Arbuckle, Hanna G. Budayeva, Ileana M. Cristea, Thomas M. Kristie

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)507-517.e5
JournalCell Host and Microbe
Volume21
Issue number4
DOIs
StatePublished - Apr 12 2017

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

Keywords

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

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