Evidence map›Paper›PMID 24788796›Full record

ArticlePLoS pathogens2014

A novel mechanism inducing genome instability in Kaposi's sarcoma-associated herpesvirus infected cells.

Brian R Jackson, Marko Noerenberg, Adrian Whitehouse

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

61 citing papers in PubMed, 79 citations in OpenAlex.

  1. Article
  2. Review
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  7. Article
  8. Article
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  10. Article
  11. Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025
    Review
  12. Review
  13. Article
  14. Regulation of R-Loops in DNA Tumor Viruses.Pathogens (Basel, Switzerland) · 2024
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Insights into the SARS-CoV-2 ORF6 Mechanism of Action.International journal of molecular sciences · 2023
    Article
  20. Review

1 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Brian R JacksonSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
Marko NoerenbergSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
Adrian WhitehouseSchool of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
Institute of Structural and Molecular Biology · GB

Funding

Biotechnology and Biological Sciences Research Council BB/K000306/1Wellcome Trust
6 · The paper itself

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus associated with multiple AIDS-related malignancies. Like other herpesviruses, KSHV has a biphasic life cycle and both the lytic and latent phases are required for tumorigenesis. Evidence suggests that KSHV lytic replication can cause genome instability in KSHV-infected cells, although no mechanism has thus far been described. A surprising link has recently been suggested between mRNA export, genome instability and cancer development. Notably, aberrations in the cellular transcription and export complex (hTREX) proteins have been identified in high-grade tumours and these defects contribute to genome instability. We have previously shown that the lytically expressed KSHV ORF57 protein interacts with the complete hTREX complex; therefore, we investigated the possible intriguing link between ORF57, hTREX and KSHV-induced genome instability. Herein, we show that lytically active KSHV infected cells induce a DNA damage response and, importantly, we demonstrate directly that this is due to DNA strand breaks. Furthermore, we show that sequestration of the hTREX complex by the KSHV ORF57 protein leads to this double strand break response and significant DNA damage. Moreover, we describe a novel mechanism showing that the genetic instability observed is a consequence of R-loop formation. Importantly, the link between hTREX sequestration and DNA damage may be a common feature in herpesvirus infection, as a similar phenotype was observed with the herpes simplex virus 1 (HSV-1) ICP27 protein. Our data provide a model of R-loop induced DNA damage in KSHV infected cells and describes a novel system for studying genome instability caused by aberrant hTREX.

Indexed as

Cell Transformation, ViralDNA Breaks, Double-StrandedGenomic InstabilityHEK293 CellsHerpesviridae InfectionsHerpesvirus 8, HumanHost-Pathogen InteractionsHumansMultiprotein ComplexesRNA, MessengerRNA TransportRNA, ViralSarcoma, KaposiSignal TransductionViral ProteinsMultiprotein ComplexesRNA, MessengerRNA, ViralViral Proteins

Identifiers

PMID24788796
PMCPMC4006916
OpenAlexW1978969477

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.