PMID- 21079815
OWN - NLM
STAT- MEDLINE
DCOM- 20110427
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 11
DP  - 2010 Nov 4
TI  - Changes to euchromatin on LAT and ICP4 following reactivation are more prevalent 
      in an efficiently reactivating strain of HSV-1.
PG  - e15416
LID - 10.1371/journal.pone.0015416 [doi]
LID - e15416
AB  - BACKGROUND: Epigenetic mechanisms, via post-translational histone modifications, 
      have roles in the establishment and maintenance of latency of the HSV-1 genome in 
      the sensory neurons. Considering that many post-translational histone marks are 
      reversible in nature, epigenetic mechanisms may also play a critical role in the 
      process of induced HSV-1 reactivation. METHODOLOGY/PRINCIPAL FINDINGS: This study 
      utilized the rabbit ocular model of HSV-1 infection and reactivation, induced by 
      the transcorneal iontophoresis of epinephrine (TCIE), to characterize changes to 
      chromatin that occur between 0.5 and 4 h following the application of the 
      reactivation stimulus. Our goal was to explore the hypothesis that chromatin 
      remodeling is an early and essential step in the process of HSV-1 reactivation. 
      Analysis of the HSV-1 latently infected rabbit trigeminal ganglia (TG) showed 
      that enrichment of the euchromatic marker H3K4me2 significantly decreased in the 
      LAT 5'exon region ( approximately 2.5-fold) and significantly increased in the lytic ICP4 
      promoter region ( approximately 3-fold) by 1 h post-TCIE in the highly efficient reactivating 
      McKrae strain of HSV-1. In contrast, we observed no significant change in the 
      euchromatic marks of H3K4me2 associated with LAT 5'exon or ICP4 promoter regions 
      of the poorly reactivating KOS strain of HSV-1 following TCIE through 4 h. The 
      implication that these observed epigenetic changes were linked to transcriptional 
      activity was confirmed by qRT-PCR examining both LAT and lytic transcript 
      abundance following TCIE. We found a significant decrease in the abundance of LAT 
      RNA by 2 h post-iontophoresis of epinephrine coupled to an increase in the 
      transcript abundance of ICP4 in the McKrae strain of HSV-1. By comparison, we 
      observed no change in the LAT or ICP4 transcript abundance of the poor 
      reactivator KOS following iontophoresis of epinephrine through 4 h. 
      CONCLUSIONS/SIGNIFICANCE: Our results implicate that chromatin remodeling is an 
      early and essential step involved in the process of in vivo HSV-1 reactivation.
FAU - Creech, Clinton C
AU  - Creech CC
AD  - Department of Ophthalmology (LSU Eye Center of Excellence), Louisiana State 
      University Health Sciences Center, New Orleans, Louisiana, United States of 
      America.
FAU - Neumann, Donna M
AU  - Neumann DM
LA  - eng
GR  - P30 EY002377/EY/NEI NIH HHS/United States
GR  - P30EY002377/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101104
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Adrenergic Agonists)
RN  - 0 (Euchromatin)
RN  - 0 (Histones)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Viral)
RN  - 0 (herpes simplex virus, type 1 protein ICP4)
RN  - 0 (latency associated transcript, herpes simplex virus-1)
RN  - K3Z4F929H6 (Lysine)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - Adrenergic Agonists/pharmacology
MH  - Animals
MH  - Chromatin Assembly and Disassembly
MH  - Cornea/metabolism/virology
MH  - Epinephrine/pharmacology
MH  - Euchromatin/*metabolism
MH  - Exons/genetics
MH  - Herpesvirus 1, Human/drug effects/*genetics/physiology
MH  - Histones/metabolism
MH  - Humans
MH  - Immediate-Early Proteins/*genetics/metabolism
MH  - Lysine/metabolism
MH  - Methylation/drug effects
MH  - MicroRNAs/*genetics/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - RNA, Viral/genetics/metabolism
MH  - Rabbits
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Trigeminal Ganglion/metabolism/virology
MH  - Virus Activation/drug effects/genetics/physiology
PMC - PMC2973973
COIS- Competing Interests: The authors have declared that no competing interests exist
EDAT- 2010/11/17 06:00
MHDA- 2011/04/28 06:00
PMCR- 2010/11/04
CRDT- 2010/11/17 06:00
PHST- 2010/08/03 00:00 [received]
PHST- 2010/09/21 00:00 [accepted]
PHST- 2010/11/17 06:00 [entrez]
PHST- 2010/11/17 06:00 [pubmed]
PHST- 2011/04/28 06:00 [medline]
PHST- 2010/11/04 00:00 [pmc-release]
AID - PONE-D-10-00263 [pii]
AID - 10.1371/journal.pone.0015416 [doi]
PST - epublish
SO  - PLoS One. 2010 Nov 4;5(11):e15416. doi: 10.1371/journal.pone.0015416.