PMID- 29514910
OWN - NLM
STAT- MEDLINE
DCOM- 20190909
LR  - 20201117
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 92
IP  - 11
DP  - 2018 Jun 1
TI  - Depletion of the Insulator Protein CTCF Results in Herpes Simplex Virus 1 
      Reactivation In Vivo.
LID - 10.1128/JVI.00173-18 [doi]
LID - e00173-18
AB  - Herpes simplex virus 1 (HSV-1) establishes a lifelong latent infection in host 
      peripheral neurons, including the neurons of the trigeminal ganglia (TG). HSV-1 
      can reactivate from neurons to cause recurrent infection. During latency, the 
      insulator protein CTCF occupies DNA binding sites on the HSV-1 genome, and these 
      sites have been previously characterized as functional enhancer-blocking 
      insulators. Previously, CTCF was found to be dissociated from wild-type virus 
      postreactivation but not in mutants that do not reactivate, indicating that CTCF 
      eviction may also be an important component of reactivation. To further elucidate 
      the role of CTCF in reactivation of HSV-1, we used recombinant adeno-associated 
      virus (rAAV) vectors to deliver a small interfering RNA targeting CTCF to 
      peripheral neurons latent with HSV-1 in rabbit TG. Our data show that CTCF 
      depletion resulted in long-term and persistent shedding of infectious virus in 
      the cornea and increased ICP0 expression in the ganglia, indicating that CTCF 
      depletion facilitates HSV-1 reactivation.IMPORTANCE Increasing evidence has shown 
      that the insulator protein CTCF regulates gene expression of DNA viruses, 
      including the gammaherpesviruses. While CTCF occupation and insulator function 
      control gene expression in DNA viruses, CTCF eviction has been correlated to 
      increased lytic gene expression and the dissolution of transcriptional domains. 
      Our previous data have shown that in the alphaherpesvirus HSV-1, CTCF was found 
      to be dissociated from the HSV-1 genome postreactivation, further indicating a 
      global role for CTCF eviction in the transition from latency to reactivation in 
      HSV-1 genomes. Using an rAAV8, we targeted HSV-1-infected peripheral neurons for 
      CTCF depletion to show that CTCF depletion precedes the shedding of infectious 
      virus and increased lytic gene expression in vivo, providing the first evidence 
      that CTCF depletion facilitates HSV-1 reactivation.
CI  - Copyright (c) 2018 American Society for Microbiology.
FAU - Washington, Shannan D
AU  - Washington SD
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, New Orleans, Louisiana, USA.
FAU - Edenfield, Samantha I
AU  - Edenfield SI
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, New Orleans, Louisiana, USA.
FAU - Lieux, Caroline
AU  - Lieux C
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, New Orleans, Louisiana, USA.
FAU - Watson, Zachary L
AU  - Watson ZL
AD  - Department of Molecular Genetics and Microbiology, University of Florida College 
      of Medicine, Gainesville, Florida, USA.
FAU - Taasan, Sean M
AU  - Taasan SM
AD  - Department of Molecular Genetics and Microbiology, University of Florida College 
      of Medicine, Gainesville, Florida, USA.
FAU - Dhummakupt, Adit
AU  - Dhummakupt A
AD  - Department of Molecular Genetics and Microbiology, University of Florida College 
      of Medicine, Gainesville, Florida, USA.
FAU - Bloom, David C
AU  - Bloom DC
AD  - Department of Molecular Genetics and Microbiology, University of Florida College 
      of Medicine, Gainesville, Florida, USA.
FAU - Neumann, Donna M
AU  - Neumann DM
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, New Orleans, Louisiana, USA dneum1@lsuhsc.edu.
AD  - Department of Ophthalmology, LSU Eye Center of Excellence, New Orleans, 
      Louisiana, USA.
LA  - eng
GR  - P30 GM106392/GM/NIGMS NIH HHS/United States
GR  - R01 AI048633/AI/NIAID NIH HHS/United States
GR  - R56 AI101174/AI/NIAID NIH HHS/United States
GR  - T32 AI007110/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180514
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CCCTC-Binding Factor)
RN  - 0 (Ctcf protein, mouse)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Binding Sites
MH  - CCCTC-Binding Factor/*genetics/metabolism
MH  - Cornea/virology
MH  - Disease Models, Animal
MH  - Ganglia/virology
MH  - Gene Knockout Techniques/*methods
MH  - Genome, Viral
MH  - Herpes Simplex/*genetics/virology
MH  - Herpesvirus 1, Human/chemistry/*physiology
MH  - Mice
MH  - Rabbits
MH  - Virus Activation
MH  - Virus Latency
MH  - Virus Shedding
PMC - PMC5952164
OTO - NOTNLM
OT  - AAV8
OT  - CTCF
OT  - HSV-1
OT  - HSV-1 reactivation
OT  - chromatin
OT  - epigenetics
OT  - gene delivery
OT  - in vivo reactivation
OT  - insulator
OT  - rabbit ocular
EDAT- 2018/03/09 06:00
MHDA- 2019/09/10 06:00
PMCR- 2018/11/14
CRDT- 2018/03/09 06:00
PHST- 2018/01/30 00:00 [received]
PHST- 2018/02/17 00:00 [accepted]
PHST- 2018/03/09 06:00 [pubmed]
PHST- 2019/09/10 06:00 [medline]
PHST- 2018/03/09 06:00 [entrez]
PHST- 2018/11/14 00:00 [pmc-release]
AID - JVI.00173-18 [pii]
AID - 00173-18 [pii]
AID - 10.1128/JVI.00173-18 [doi]
PST - epublish
SO  - J Virol. 2018 May 14;92(11):e00173-18. doi: 10.1128/JVI.00173-18. Print 2018 Jun 
      1.