Restarting Lytic Gene Transcription at the Onset of Herpes Simplex Virus Reactivation

J Virol. 2017 Jan 3;91(2):e01419-16. doi: 10.1128/JVI.01419-16. Print 2017 Jan 15.


Herpes simplex virus (HSV) establishes a latent reservoir in neurons of human peripheral nerves. In this quiescent state, the viral genome persists as a circular, histone-associated episome, and transcription of viral lytic cycle genes is largely suppressed through epigenetic processes. Periodically, latent virus undergoes reactivation whereby lytic genes are activated and viral replication occurs. In this Gem, we review recent evidence that mechanisms governing the initial transcription of lytic genes are distinct from those of de novo infection and directly link reactivation to neuronal stress response pathways. We also discuss evidence that lytic cycle gene expression can be uncoupled from the full reactivation program, arguing for a less sharply bimodal definition of latency.

Keywords: JNK signaling; episome; herpes simplex virus; heterochromatin; histone methylation; latency; neurotropic viruses; reactivation; transcriptional regulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Viral*
  • Herpes Simplex / metabolism
  • Herpes Simplex / virology*
  • Host-Pathogen Interactions
  • Humans
  • Neurons / metabolism
  • Neurons / virology
  • Signal Transduction / drug effects
  • Simplexvirus / physiology*
  • Stress, Physiological
  • Transcription, Genetic*
  • Virus Activation*
  • Virus Latency
  • Virus Replication*