PMID- 29563516
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20210109
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Mar 21
TI  - A spliced latency-associated VZV transcript maps antisense to the viral 
      transactivator gene 61.
PG  - 1167
LID - 10.1038/s41467-018-03569-2 [doi]
LID - 1167
AB  - Varicella-zoster virus (VZV), an alphaherpesvirus, establishes lifelong latent 
      infection in the neurons of >90% humans worldwide, reactivating in one-third to 
      cause shingles, debilitating pain and stroke. How VZV maintains latency remains 
      unclear. Here, using ultra-deep virus-enriched RNA sequencing of latently 
      infected human trigeminal ganglia (TG), we demonstrate the consistent expression 
      of a spliced VZV mRNA, antisense to VZV open reading frame 61 (ORF61). The 
      spliced VZV latency-associated transcript (VLT) is expressed in human TG neurons 
      and encodes a protein with late kinetics in productively infected cells in vitro 
      and in shingles skin lesions. Whereas multiple alternatively spliced VLT isoforms 
      (VLT(ly)) are expressed during lytic infection, a single unique VLT isoform, 
      which specifically suppresses ORF61 gene expression in co-transfected cells, 
      predominates in latently VZV-infected human TG. The discovery of VLT links VZV 
      with the other better characterized human and animal neurotropic 
      alphaherpesviruses and provides insights into VZV latency.
FAU - Depledge, Daniel P
AU  - Depledge DP
AUID- ORCID: 0000-0002-4292-0599
AD  - Division of Infection and Immunity, University College London, London, WC1E 6BT, 
      UK.
AD  - Department of Microbiology, New York University, New York, NY, 10016, USA.
FAU - Ouwendijk, Werner J D
AU  - Ouwendijk WJD
AD  - Department of Viroscience, Erasmus Medical Centre, 3015 CN, Rotterdam, The 
      Netherlands.
FAU - Sadaoka, Tomohiko
AU  - Sadaoka T
AUID- ORCID: 0000-0001-7951-6904
AD  - Division of Clinical Virology, Center for Infectious Diseases, Kobe University 
      Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
FAU - Braspenning, Shirley E
AU  - Braspenning SE
AD  - Department of Viroscience, Erasmus Medical Centre, 3015 CN, Rotterdam, The 
      Netherlands.
FAU - Mori, Yasuko
AU  - Mori Y
AD  - Division of Clinical Virology, Center for Infectious Diseases, Kobe University 
      Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
FAU - Cohrs, Randall J
AU  - Cohrs RJ
AD  - Department of Neurology, University of Colorado School of Medicine, Aurora, CO, 
      12700, USA.
AD  - Department of Immunology & Microbiology, University of Colorado School of 
      Medicine, Aurora, CO, 12800, USA.
FAU - Verjans, Georges M G M
AU  - Verjans GMGM
AD  - Department of Viroscience, Erasmus Medical Centre, 3015 CN, Rotterdam, The 
      Netherlands. g.verjans@erasmusmc.nl.
AD  - Research Centre for Emerging Infections and Zoonoses, University of Veterinary 
      Medicine Hannover, 30559, Hannover, Germany. g.verjans@erasmusmc.nl.
FAU - Breuer, Judith
AU  - Breuer J
AUID- ORCID: 0000-0001-8246-0534
AD  - Division of Infection and Immunity, University College London, London, WC1E 6BT, 
      UK. j.breuer@ucl.ac.uk.
LA  - eng
GR  - R01 NS093716/NS/NINDS NIH HHS/United States
GR  - R01 NS082228/NS/NINDS NIH HHS/United States
GR  - G0700814/MRC_/Medical Research Council/United Kingdom
GR  - P01 AG032958/AG/NIA NIH HHS/United States
GR  - G0900950/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180321
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (DNA, Viral)
RN  - 0 (RNA, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Viral)
RN  - 0 (Viral Proteins)
RN  - 106121-63-5 (protein 61, Varicella-zoster virus)
SB  - IM
MH  - Animals
MH  - Chromosome Mapping
MH  - DNA, Viral/genetics/metabolism
MH  - Genome, Viral
MH  - Herpes Zoster/pathology/*virology
MH  - Herpesvirus 3, Human/*genetics/metabolism/pathogenicity
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Neurons/pathology/virology
MH  - RNA Splicing
MH  - RNA, Antisense/*genetics/metabolism
MH  - RNA, Messenger/*genetics/metabolism
MH  - RNA, Viral/*genetics/metabolism
MH  - Skin/pathology/virology
MH  - Trigeminal Ganglion/pathology/virology
MH  - Viral Proteins/antagonists & inhibitors/*genetics/metabolism
MH  - *Virus Latency
PMC - PMC5862956
COIS- The authors declare no competing interests.
EDAT- 2018/03/23 06:00
MHDA- 2018/12/12 06:00
PMCR- 2018/03/21
CRDT- 2018/03/23 06:00
PHST- 2017/12/01 00:00 [received]
PHST- 2018/02/23 00:00 [accepted]
PHST- 2018/03/23 06:00 [entrez]
PHST- 2018/03/23 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/03/21 00:00 [pmc-release]
AID - 10.1038/s41467-018-03569-2 [pii]
AID - 3569 [pii]
AID - 10.1038/s41467-018-03569-2 [doi]
PST - epublish
SO  - Nat Commun. 2018 Mar 21;9(1):1167. doi: 10.1038/s41467-018-03569-2.