| Title: |
Varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene expression during reactivation from neuronal latency. |
| Authors: |
Ouwendijk, Werner J. D., Depledge, Daniel P., Rajbhandari, Labchan, Lenac Rovis, Tihana, Jonjic, Stipan, Breuer, Judith, Venkatesan, Arun, Verjans, Georges M. G. M., Sadaoka, Tomohiko |
| Source: |
Nature Communications; 12/10/2020, Vol. 11 Issue 1, p1-12, 12p |
| Subject Terms: |
VARICELLA-zoster virus, VIRAL genes, GENE expression, CHIMERIC proteins, HERPES zoster, CHRONIC pain, VARICELLA-zoster virus diseases |
| Abstract: |
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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
