{"doi":"10.1101/2020.09.11.294280","title":"Expression of varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene expression during reactivation from neuronal latency","abstract":"Summary 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. Latent VZV gene expression is restricted to VZV latency-associated transcript (VLT) and open reading frame 63 (ORF63) in naturally VZV-infected human trigeminal ganglia (TG). Notably, these transcript levels positively correlated suggesting co-regulated transcription during latency. Here, we used direct RNA-sequencing to identify fusion transcripts that combine VLT and ORF63 loci (VLT-ORF63) and are expressed during both lytic and latent VZV infections. Furthermore, real-time PCR, RNA in situ hybridization and 5’ rapid amplification of cDNA ends (RACE) all confirmed VLT-ORF63, but not canonical ORF63, expression in human TG. During lytic infection, one of the two major VLT-ORF63 isoforms encodes a novel fusion protein combining VLT and ORF63 proteins (pVLT-ORF63). In vitro , VLT is transcribed in latently VZV-infected human sensory neurons, whereas VLT-ORF63 expression is induced by reactivation stimuli. Moreover, the pVLT-ORF63-encoding VLT-ORF63 isoform induced transcription of lytic VZV genes. 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124039,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":244833,"name":"Daniel P. Depledge","orcid":"0000-0002-4292-0599","position":1,"is_corresponding":false},{"id":328899,"name":"Labchan Rajbhandari","orcid":"0000-0002-9252-2580","position":2,"is_corresponding":false},{"id":328900,"name":"T. Rovis","orcid":"0000-0002-3299-1334","position":3,"is_corresponding":false},{"id":328901,"name":"Stipan Jonjić","orcid":"0000-0001-5003-3108","position":4,"is_corresponding":false},{"id":289016,"name":"Judith Breuer","orcid":"0000-0001-8246-0534","position":5,"is_corresponding":false},{"id":328902,"name":"Arun Venkatesan","orcid":"0000-0002-9335-7361","position":6,"is_corresponding":false},{"id":305737,"name":"Georges M. G. M. Verjans","orcid":"0000-0002-2465-2674","position":7,"is_corresponding":false},{"id":305736,"name":"Tomohiko Sadaoka","orcid":"0000-0001-7951-6904","position":8,"is_corresponding":false},{"id":305738,"name":"Werner J. D. Ouwendijk","orcid":"0000-0001-8393-296X","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}