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A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61.

Daniel P Depledge | Werner J D Ouwendijk | Tomohiko Sadaoka | Shirley E Braspenning | Yasuko Mori | Randall J Cohrs | Georges M G M Verjans | Judith Breuer
Nature communications | 2018

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.

Pubmed ID: 29563516

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS093716
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS082228
  • Agency: Medical Research Council, United Kingdom
    Id: G0700814
  • Agency: NIA NIH HHS, United States
    Id: P01 AG032958
  • Agency: Medical Research Council, United Kingdom
    Id: G0900950

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RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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RRID:SCR_008406

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RRID:SCR_008452

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RRID:SCR_001913

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RRID:SCR_006515

Public archive providing a comprehensive record of the world''''s nucleotide sequencing information, covering raw sequencing data, sequence assembly information and functional annotation. All submitted data, once public, will be exchanged with the NCBI and DDBJ as part of the INSDC data exchange agreement. The European Nucleotide Archive (ENA) captures and presents information relating to experimental workflows that are based around nucleotide sequencing. A typical workflow includes the isolation and preparation of material for sequencing, a run of a sequencing machine in which sequencing data are produced and a subsequent bioinformatic analysis pipeline. ENA records this information in a data model that covers input information (sample, experimental setup, machine configuration), output machine data (sequence traces, reads and quality scores) and interpreted information (assembly, mapping, functional annotation). Data arrive at ENA from a variety of sources including submissions of raw data, assembled sequences and annotation from small-scale sequencing efforts, data provision from the major European sequencing centers and routine and comprehensive exchange with their partners in the International Nucleotide Sequence Database Collaboration (INSDC). Provision of nucleotide sequence data to ENA or its INSDC partners has become a central and mandatory step in the dissemination of research findings to the scientific community. ENA works with publishers of scientific literature and funding bodies to ensure compliance with these principles and to provide optimal submission systems and data access tools that work seamlessly with the published literature. ENA is made up of a number of distinct databases that includes the EMBL Nucleotide Sequence Database (Embl-Bank), the newly established Sequence Read Archive (SRA) and the Trace Archive. The main tool for downloading ENA data is the ENA Browser, which is available through REST URLs for easy programmatic use. All ENA data are available through the ENA Browser. Note: EMBL Nucleotide Sequence Database (EMBL-Bank) is entirely included within this resource.

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RRID:SCR_006525

Java toolset for working with next generation sequencing data in the BAM format.

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Trim Galore (tool)

RRID:SCR_011847

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Netherlands Brain Bank (tool)

RRID:SCR_013841

A biomaterial supply resource which collects, stores, and disseminates diseased and healthy brain tissue. The Netherlands Brain Bank currently contains more than 3600 samples, and each sample includes a neuropathological report and donor medical history. The samples can additionally be matched with ante-mortem parameters and post-mortem parameters upon request. Sample types include cortex, spinal cord, cerebrospinal fluid, plasma, and DNA, among others. Database mining is available with a financial contribution.

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ShortStack (tool)

RRID:SCR_010834

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featureCounts (tool)

RRID:SCR_012919

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RRID:SCR_013517

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RRID:SCR_013530

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RRID:SCR_014199

Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.

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ARPE-19 (tool)

RRID:CVCL_0145

Cell line ARPE-19 is a Spontaneously immortalized cell line with a species of origin Homo sapiens (Human)

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