3 research outputs found
Decoding the Architecture of the Varicella-Zoster Virus Transcriptome
Varicella-zoster virus (VZV), a double-stranded DNA virus, causes varicella, establishes lifelong latency in ganglionic neurons, and reactivates later in life
to cause herpes zoster, commonly associated with chronic pain. The VZV genome is
densely packed and produces multitudes of overlapping transcripts deriving from
both strands. While 71 distinct open reading frames (ORFs) have thus far been experimentally defined, the full coding potential of VZV remains unknown. Here, we
integrated multiple short-read RNA sequencing approaches with long-read direct
RNA sequencing on RNA isolated from VZV-infected cells to provide a comprehensive reannotation of the lytic VZV transcriptome architecture. Through precise mapping of transcription start sites, splice junctions, and polyadenylation
sites, we identified 136 distinct polyadenylated VZV RNAs that encode canonical
ORFs, noncanonical ORFs, and ORF fusions, as well as putative noncoding RNAs
(ncRNAs). Furthermore, we determined the kinetic class of all VZV transcri
A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene
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 (VLTly) 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
Uniform Registration Agreements on Cholesteatoma Care: A Nationwide Consensus Procedure
Background: To coordinate and align the content for
registration of cholesteatoma care.
Methods: Systematic Delphi consensus procedure, consisting
three rounds: two written sessions followed by a face-to-face
meeting. Before this procedure, input on important patient
outcomes was obtained. Consensus was defined as at least
80% agreement by participants. Hundred-thirty-six adult
patients who had undergone cholesteatoma surgery and
all ENT surgeons of the Dutch ENT Society were invited. The
consensus rounds were att