RRC ID 67112
Author Ouwendijk WJD, Depledge DP, Rajbhandari L, Lenac Rovis T, Jonjic S, Breuer J, Venkatesan A, Verjans GMGM, Sadaoka T.
Title Varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene expression during reactivation from neuronal latency.
Journal Nat Commun
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.
Volume 11(1)
Pages 6324
Published 2020-12-10
DOI 10.1038/s41467-020-20031-4
PII 10.1038/s41467-020-20031-4
PMID 33303747
PMC PMC7730162
MeSH Anisomycin / pharmacology Gene Expression Regulation, Viral* Herpesvirus 3, Human / genetics* Humans JNK Mitogen-Activated Protein Kinases / metabolism Open Reading Frames / genetics Protein Isoforms / genetics Protein Isoforms / metabolism RNA, Messenger / genetics RNA, Messenger / metabolism Sensory Receptor Cells / virology* Transcription, Genetic / drug effects Trigeminal Ganglion / pathology Trigeminal Ganglion / virology Viral Proteins / genetics* Viral Proteins / metabolism Virus Activation / genetics* Virus Latency / genetics*
IF 12.121
DNA material CS-CA-MCS (RDB05963) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)