| 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
|
| Resource |
| DNA material |
CS-CA-MCS (RDB05963)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394) |
