PMID- 33303747
OWN - NLM
STAT- MEDLINE
DCOM- 20201228
LR  - 20240331
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Dec 10
TI  - Varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene 
      expression during reactivation from neuronal latency.
PG  - 6324
LID - 10.1038/s41467-020-20031-4 [doi]
LID - 6324
AB  - Varicella-zoster virus (VZV) establishes lifelong neuronal latency in most humans 
      world-wide, reactivating in one-third to cause herpes zoster and occasionally 
      chronic pain. How VZV establishes, maintains and reactivates from latency is 
      largely unknown. VZV transcription during latency is restricted to the 
      latency-associated transcript (VLT) and RNA 63 (encoding ORF63) in naturally 
      VZV-infected human trigeminal ganglia (TG). While significantly more abundant, 
      VLT levels positively correlated with RNA 63 suggesting co-regulated 
      transcription during latency. Here, we identify VLT-ORF63 fusion transcripts and 
      confirm VLT-ORF63, but not RNA 63, expression in human TG neurons. During in 
      vitro latency, VLT is transcribed, whereas VLT-ORF63 expression is induced by 
      reactivation stimuli. One isoform of VLT-ORF63, encoding a fusion protein 
      combining VLT and ORF63 proteins, induces broad viral gene transcription. 
      Collectively, our findings show that VZV expresses a unique set of VLT-ORF63 
      transcripts, potentially involved in the transition from latency to lytic VZV 
      infection.
FAU - Ouwendijk, Werner J D
AU  - Ouwendijk WJD
AUID- ORCID: 0000-0001-8393-296X
AD  - Department of Viroscience, Erasmus Medical Centre, 3015 CN, Rotterdam, The 
      Netherlands.
FAU - Depledge, Daniel P
AU  - Depledge DP
AD  - Department of Medicine, New York University School of Medicine, New York, NY, 
      10016, USA.
FAU - Rajbhandari, Labchan
AU  - Rajbhandari L
AUID- ORCID: 0000-0002-9252-2580
AD  - Division of Neuroimmunology and Neuroinfectious Diseases, Department of 
      Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Meyer 
      6-113, Baltimore, MD, 21287, USA.
FAU - Lenac Rovis, Tihana
AU  - Lenac Rovis T
AD  - Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, 51000, 
      Croatia.
FAU - Jonjic, Stipan
AU  - Jonjic S
AUID- ORCID: 0000-0001-5003-3108
AD  - Center for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, 51000, 
      Croatia.
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.
FAU - Venkatesan, Arun
AU  - Venkatesan A
AD  - Division of Neuroimmunology and Neuroinfectious Diseases, Department of 
      Neurology, Johns Hopkins University School of Medicine, 600 N. Wolfe St., Meyer 
      6-113, Baltimore, MD, 21287, USA.
FAU - Verjans, Georges M G M
AU  - Verjans GMGM
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. 
      tomsada@crystal.kobe-u.ac.jp.
LA  - eng
GR  - R01 GM056927/GM/NIGMS NIH HHS/United States
GR  - G0700814/MRC_/Medical Research Council/United Kingdom
GR  - DH_/Department of Health/United Kingdom
GR  - R01 AI151290/AI/NIAID NIH HHS/United States
GR  - R21 NS107991/NS/NINDS NIH HHS/United States
GR  - R01 AI152543/AI/NIAID NIH HHS/United States
GR  - R01 AI073898/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 - 20201210
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 0 (Viral Proteins)
RN  - 6C74YM2NGI (Anisomycin)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Anisomycin/pharmacology
MH  - *Gene Expression Regulation, Viral
MH  - Herpesvirus 3, Human/*genetics
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - Open Reading Frames/genetics
MH  - Protein Isoforms/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Sensory Receptor Cells/*virology
MH  - Transcription, Genetic/drug effects
MH  - Trigeminal Ganglion/pathology/virology
MH  - Viral Proteins/*genetics/metabolism
MH  - Virus Activation/*genetics
MH  - Virus Latency/*genetics
PMC - PMC7730162
COIS- The authors declare no competing interests.
EDAT- 2020/12/12 06:00
MHDA- 2020/12/29 06:00
PMCR- 2020/12/10
CRDT- 2020/12/11 05:51
PHST- 2020/03/20 00:00 [received]
PHST- 2020/11/10 00:00 [accepted]
PHST- 2020/12/11 05:51 [entrez]
PHST- 2020/12/12 06:00 [pubmed]
PHST- 2020/12/29 06:00 [medline]
PHST- 2020/12/10 00:00 [pmc-release]
AID - 10.1038/s41467-020-20031-4 [pii]
AID - 20031 [pii]
AID - 10.1038/s41467-020-20031-4 [doi]
PST - epublish
SO  - Nat Commun. 2020 Dec 10;11(1):6324. doi: 10.1038/s41467-020-20031-4.