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A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61
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A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61
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A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61
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Journal Article
A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61
2018
Overview
Varicella-zoster virus (VZV), an alphaherpesvirus, establishes lifelong latent infection in the neurons of >90% humans worldwide, reactivating in one-third to cause shingles, debilitating pain and stroke. How VZV maintains latency remains unclear. Here, using ultra-deep virus-enriched RNA sequencing of latently infected human trigeminal ganglia (TG), we demonstrate the consistent expression of a spliced VZV mRNA, antisense to VZV open reading frame 61 (ORF61). The spliced VZV latency-associated transcript (VLT) is expressed in human TG neurons and encodes a protein with late kinetics in productively infected cells in vitro and in shingles skin lesions. Whereas multiple alternatively spliced VLT isoforms (VLT
ly
) are expressed during lytic infection, a single unique VLT isoform, which specifically suppresses ORF61 gene expression in co-transfected cells, predominates in latently VZV-infected human TG. The discovery of VLT links VZV with the other better characterized human and animal neurotropic alphaherpesviruses and provides insights into VZV latency.
Varicella-zoster virus (VZV) establishes lifelong infection in the majority of the population, but mechanisms underlying latency remain unclear. Here, the authors use ultra-deep RNA sequencing, enriched for viral RNAs, of latently infected human trigeminal ganglia and identify a spliced, latency-associated VZV mRNA.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/77
/ 45/88
/ 45/90
/ 45/91
/ Animals
/ Ganglia
/ Herpesvirus 3, Human - genetics
/ Herpesvirus 3, Human - metabolism
/ Herpesvirus 3, Human - pathogenicity
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ Isoforms
/ Latency
/ Lesions
/ Neurons
/ Pain
/ RNA
/ Science
/ Trigeminal Ganglion - pathology
/ Trigeminal Ganglion - virology
/ Viral Proteins - antagonists & inhibitors
/ Viruses
