Restarting Lytic Gene Transcription at the Onset of Herpes Simplex Virus Reactivation.
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.
Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, Virginia, USA.
Anna R
http://orcid.org/0000-0003-1136-5171
AR
Cliffe
Department of Microbiology, New York University School of Medicine, New York, New York, USA angus.wilson@med.nyu.edu.
Angus C
http://orcid.org/0000-0002-5016-4164
AC
Wilson
D000818:Animals; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000821:virology; D015398:Signal Transduction / Q000187:drug effects; D018139:Simplexvirus / Q000502:physiology*; D013312:Stress, Physiological; D014158:Transcription, Genetic; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
JNK signaling; episome; herpes simplex virus; heterochromatin; histone methylation; latency; neurotropic viruses; reactivation; transcriptional regulation