PMID- 25645379
OWN - NLM
STAT- MEDLINE
DCOM- 20151229
LR  - 20181113
IS  - 1538-2443 (Electronic)
IS  - 1355-0284 (Print)
IS  - 1355-0284 (Linking)
VI  - 21
IP  - 2
DP  - 2015 Apr
TI  - A herpes simplex virus type 1 mutant disrupted for microRNA H2 with increased 
      neurovirulence and rate of reactivation.
PG  - 199-209
LID - 10.1007/s13365-015-0319-1 [doi]
AB  - The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) 
      encodes several microRNAs. One of these, miR-H2, overlaps and is antisense to the 
      ICP0 gene and appears to decrease expression of the ICP0 protein. To determine if 
      miR-H2 plays a role in the HSV-1 latency-reactivation cycle, we constructed a 
      mutant, McK-DeltaH2, in which this microRNA has been disrupted without altering the 
      predicted amino acid sequence of ICP0. McK-DeltaH2 produced increased amounts of 
      ICP0. Although replication of McK-DeltaH2 was similar to that of its wild-type (wt) 
      McKrae parental virus in RS cells and mouse eyes, McK-DeltaH2 was more neurovirulent 
      in Swiss-Webster mice than McKrae based on the percent of mice that died from 
      herpes encephalitis following ocular infection. In addition, using a mouse 
      trigeminal ganglia (TG) explant model of induced reactivation, we show here for 
      the first time that miR-H2 appears to play a role in modulating HSV-1 
      reactivation. Although the percent of TG from which virus reactivated by day 10 
      after explant was similar for McK-DeltaH2, wt McKrae, and the marker-rescued virus 
      McK-DeltaH2Res, at earlier times, significantly more reactivation was seen with 
      McK-DeltaH2. Our results suggest that in the context of the virus, miR-H2 
      downregulates ICP0 and this moderates both HSV-1 neurovirulence and reactivation.
FAU - Jiang, Xianzhi
AU  - Jiang X
AD  - Virology Research, Gavin Herbert Eye Institute and Department of Ophthalmology, 
      School of Medicine, University of California, Irvine, 843 Health Sciences Road, 
      Hewitt Hall (Building 843), Room 2012, Irvine, CA, 92697, USA.
FAU - Brown, Don
AU  - Brown D
FAU - Osorio, Nelson
AU  - Osorio N
FAU - Hsiang, Chinhui
AU  - Hsiang C
FAU - Li, Lily
AU  - Li L
FAU - Chan, Lucas
AU  - Chan L
FAU - BenMohamed, Lbachir
AU  - BenMohamed L
FAU - Wechsler, Steven L
AU  - Wechsler SL
LA  - eng
GR  - R56 AI098985/AI/NIAID NIH HHS/United States
GR  - R01 EY013191/EY/NEI NIH HHS/United States
GR  - R56 AI093133/AI/NIAID NIH HHS/United States
GR  - R01 EY019896/EY/NEI NIH HHS/United States
GR  - R01EY14900/EY/NEI NIH HHS/United States
GR  - R01EY019896/EY/NEI NIH HHS/United States
GR  - R01EY013191/EY/NEI NIH HHS/United States
GR  - 1R56AI098985/AI/NIAID NIH HHS/United States
GR  - UL1 TR001414/TR/NCATS NIH HHS/United States
GR  - R01 EY014900/EY/NEI NIH HHS/United States
GR  - 1R56AI093133/AI/NIAID NIH HHS/United States
GR  - R01 EY024618/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150203
PL  - United States
TA  - J Neurovirol
JT  - Journal of neurovirology
JID - 9508123
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Viral)
RN  - 0 (latency associated transcript, herpes simplex virus-1)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (Vmw110 protein, Human herpesvirus 1)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression Regulation, Viral/*genetics
MH  - Herpes Simplex/*genetics
MH  - Herpesvirus 1, Human/pathogenicity/physiology
MH  - Immediate-Early Proteins/biosynthesis/genetics
MH  - Immunoblotting
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - MicroRNAs/*genetics
MH  - RNA, Viral/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ubiquitin-Protein Ligases/biosynthesis/genetics
MH  - Virulence
MH  - Virus Activation/*genetics
MH  - Virus Latency/genetics
PMC - PMC4375036
MID - NIHMS660769
EDAT- 2015/02/04 06:00
MHDA- 2015/12/30 06:00
PMCR- 2016/04/01
CRDT- 2015/02/04 06:00
PHST- 2014/11/21 00:00 [received]
PHST- 2015/01/09 00:00 [accepted]
PHST- 2014/12/19 00:00 [revised]
PHST- 2015/02/04 06:00 [entrez]
PHST- 2015/02/04 06:00 [pubmed]
PHST- 2015/12/30 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - 10.1007/s13365-015-0319-1 [doi]
PST - ppublish
SO  - J Neurovirol. 2015 Apr;21(2):199-209. doi: 10.1007/s13365-015-0319-1. Epub 2015 
      Feb 3.