Evidence map›Paper›PMID 25071216›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Kaposi's sarcoma-associated herpesvirus LANA recruits the DNA polymerase clamp loader to mediate efficient replication and virus persistence.

Qiming Sun, Toshiki Tsurimoto, Franceline Juillard, Lin Li, Shijun Li, Erika De León Vázquez, She Chen, Kenneth Kaye

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

33 citing papers in PubMed, 45 citations in OpenAlex.

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  8. Article
  9. Structure of the human clamp loader reveals an autoinhibited conformation of a substrate-bound AAA+ switch.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  10. KSHV LANA acetylation-selective acidic domain reader sequence mediates virus persistence.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  11. Article
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  15. Serological Assessment of 18 Pathogens and Risk of AIDS-Associated Non-Hodgkin Lymphoma.Journal of acquired immune deficiency syndromes (1999) · 2019
    Article
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4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

8 authors at 4 institutions in 3 countries.

Qiming SunDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Toshiki TsurimotoDepartment of Biology, Kyushu University, Fukuoka 812-8581, Japan; and.
Franceline JuillardDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Lin LiProteomics Center, National Institute of Biological Sciences, Beijing 102206, People's Republic of China.
Shijun LiDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
Erika De León VázquezDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115;
She ChenProteomics Center, National Institute of Biological Sciences, Beijing 102206, People's Republic of China.
Kenneth KayeDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; kkaye@rics.bwh.harvard.edu.
Harvard University · USBrigham and Women's Hospital · USNational Institute of Biological Sciences, Beijing · CNKyushu University · JP

Funding

GENETIC AND BIOCHEMICAL STUDIES OF THE KSHV LANA GENER01CA082036 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KAYE, KENNETH M · 1999 to 2019
$7.6M
NCI NIH HHS CA082036NCI NIH HHS R01 CA082036
6 · The paper itself

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) latently infects tumor cells and persists as a multiple-copy, extrachromosomal, circular episome. To persist, the viral genome must replicate with each cell cycle. The KSHV latency-associated nuclear antigen (LANA) mediates viral DNA replication and persistence, but little is known regarding the underlying mechanisms. We find that LANA recruits replication factor C (RFC), the DNA polymerase clamp [proliferating cell nuclear antigen (PCNA)] loader, to drive DNA replication efficiently. Mutated LANA lacking RFC interaction was deficient for LANA-mediated DNA replication and episome persistence. RFC depletion had a negative impact on LANA's ability to replicate and maintain viral DNA in cells containing artificial KSHV episomes or in infected cells, leading to loss of virus. LANA substantially increased PCNA loading onto DNA in vitro and recruited RFC and PCNA to KSHV DNA in cells. These findings suggest that PCNA loading is a rate-limiting step in DNA replication that is incompatible with viral survival. LANA enhancement of PCNA loading permits efficient virus replication and persistence, revealing a previously unidentified mechanism for KSHV latency.

Indexed as

Antigens, ViralCell Line, TumorDNA-Directed DNA PolymeraseDNA ReplicationDNA, ViralGene Knockdown TechniquesHerpesvirus 8, HumanHost-Pathogen InteractionsHumansNuclear ProteinsProliferating Cell Nuclear AntigenReplication Protein CSarcoma, KaposiVirus LatencyVirus ReplicationAntigens, ViralDNA-Directed DNA PolymeraseDNA, Virallatency-associated nuclear antigenNuclear ProteinsProliferating Cell Nuclear AntigenReplication Protein CRFC1 protein, human

Identifiers

PMID25071216
PMCPMC4136584
OpenAlexW2045437181

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.