Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-020-20031-4
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Funding
- Takeda Science Foundation
- Japan Society for the Promotion of Science (JSPS KAKENHI) [JP17K008858, JP16H06429, JP16K21723]
- Ministry of Education, Culture, Sports, Science and Technology (MEXT KAKENHI) [JP17H05816]
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01AI151290]
- NIH [R01GM056927, R01AI073898, R01AI152543]
- NIH NINDS [R21NS107991]
- UCL/UCLH NIHR Biomedical Research Centre [KK.01.1.1.01.0006]
- European Regional Development Fund
- Daiichi Sankyo Foundation of Life Science
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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. Varicella-zoster virus (VZV) establishes lifelong neuronal latency in humans. Here, Ouwendijk and Depledge et al. identify a fusion transcript, VLT-ORF63, which is expressed during lytic and latent infection, and demonstrate a role for the translated fusion protein in induction of lytic gene expression from latent VZV genomes.
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