Evidence map›Paper›PMID 30682185›Full record

ArticlePLoS pathogens2019

LANA oligomeric architecture is essential for KSHV nuclear body formation and viral genome maintenance during latency.

Alessandra De Leo, Zhong Deng, Olga Vladimirova, Horng-Shen Chen, Jayaraju Dheekollu, Abram Calderon, Kenneth A Myers, James Hayden, Frederick Keeney, Benedikt B Kaufer and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 41 citations in OpenAlex.

  1. Article
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  6. Molecular Mechanisms of KSHV Latency Establishment and Maintenance.Current clinical microbiology reports · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Alessandra De LeoProgram in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Zhong DengProgram in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Olga VladimirovaProgram in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Horng-Shen ChenProgram in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Jayaraju DheekolluProgram in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Abram CalderonProgram in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Kenneth A MyersDepartment of Biological Sciences, University of the Sciences, Philadelphia, Pennsylvania, United States of America.
James HaydenProgram in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Frederick KeeneyProgram in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.
Benedikt B KauferDepartment of Virology, Institute Virology, Freie Universitat Berlin, Berlin, Germany.ORCID 0000-0003-1328-2695
Yan YuanDepartment of Biochemistry, School of Dentistry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Erle RobertsonDepartment of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Paul M LiebermanProgram in Gene Expression and Regulation, The Wistar Institute, Philadelphia, Pennsylvania, United States of America.ORCID 0000-0002-3935-9921
The Wistar Institute · USUniversity of Pennsylvania · USFreie Universität Berlin · DEUniversity of the Sciences · US

Funding

Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Aaron Robert Goldman · 1985 to 2026
$75.9M
TRAINING PROGRAM IN BASIC CANCER RESEARCHT32CA009171 · NCI · WISTAR INSTITUTE · PI Alessandro Gardini · 1985 to 2026
$15.3M
Role of LANA-RBP-jk During Early KSHV InfectionP01CA174439 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROBERTSON, ERLE S. · 2013 to 2018
$8.7M
Regulation of KSHV LatencyR01CA117830 · NCI · WISTAR INSTITUTE · PI PAUL M. LIEBERMAN · 2006 to 2026
$6.4M
Development of a Small Molecule Inhibitor for KSHV LANAR01CA186775 · NCI · WISTAR INSTITUTE · PI LIEBERMAN, PAUL M. · 2014 to 2018
$2.0M
NCI NIH HHS P01 CA174439NCI NIH HHS P30 CA010815NCI NIH HHS R01 CA117830NCI NIH HHS R01 CA186775NCI NIH HHS T32 CA009171
6 · The paper itself

Abstract

The molecular basis for the formation of functional, higher-ordered macro-molecular domains is not completely known. The Kaposi's Sarcoma-Associated Herpesvirus (KSHV) genome forms a super-molecular domain structure during latent infection that is strictly dependent on the DNA binding of the viral nuclear antigen LANA to the viral terminal repeats (TR). LANA is known to form oligomeric structures that have been implicated in viral episome maintenance. In this study, we show that the LANA oligomerization interface is required for the formation of higher-order nuclear bodies that partially colocalize with DAXX, EZH2, H3K27me3, and ORC2 but not with PML. These nuclear bodies assemble at the periphery of condensed cellular chromosomes during mitotic cell division. We demonstrate that the LANA oligomerization interface contributes to the cooperative DNA binding at the viral TR and the recruitment of ORC to the viral episome. Oligomerization mutants failed to auto-regulate LANA/ORF73 transcription, and this correlated with the loss of a chromosome conformational DNA-loop between the TR and LANA promoter. Viral genomes with LANA oligomerization mutants were subject to genome rearrangements including the loss of subgenomic DNA. Our data suggests that LANA oligomerization drives stable binding to the TR and formation of an epigenetically stable chromatin architecture resulting in higher-order LANA nuclear bodies important for viral genome integrity and long-term episome persistence.

Indexed as

Adaptor Proteins, Signal TransducingAntigens, ViralCell LineCell NucleusChromatinChromosomesCo-Repressor ProteinsDNA ReplicationDNA, ViralEnhancer of Zeste Homolog 2 ProteinGenome, ViralHerpesvirus 8, HumanHumansIntranuclear Inclusion BodiesMolecular ChaperonesNuclear ProteinsAdaptor Proteins, Signal TransducingAntigens, ViralChromatinCo-Repressor ProteinsDAXX protein, humanDNA, ViralEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanlatency-associated nuclear antigenMolecular ChaperonesNuclear ProteinsOrigin Recognition Complex

Identifiers

PMID30682185
PMCPMC6364946
OpenAlexW2911543110

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.