Evidence map›Paper›PMID 19131434›Full record

ArticleGenes & development2009

Robust production and passaging of infectious HPV in squamous epithelium of primary human keratinocytes.

Hsu-Kun Wang, Aaron A Duffy, Thomas R Broker, Louise T Chow

Abstract read
In one paragraph

Article in Genes & development, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

104 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  12. Downregulation of Sonic hedgehog signaling induces G2-arrest in genital warts.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2023
    Article
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  19. Oncogenic HPV promotes the expression of the long noncoding RNA lnc-FANCI-2 through E7 and YY1.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Hsu-Kun WangDepartment of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Aaron A Duffy
Thomas R Broker
Louise T Chow

Funding

MECHANISMS OF HUMAN PAPILLOMAVIRUS DNA REPLICATIONR01CA083679 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CHOW, LOUISE T · 1999 to 2015
$5.1M
Mechanisms of HPV DNA SegregationR01CA107338 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CHOW, LOUISE T · 2004 to 2008
$1.7M
NCI NIH HHS CA107338NCI NIH HHS CA83679NCI NIH HHS R01 CA083679NCI NIH HHS R01 CA107338
6 · The paper itself

Abstract

Using Cre-loxP-mediated recombination, we established a highly efficient and reproducible system that generates autonomous HPV-18 genomes in primary human keratinocytes (PHKs), the organotypic raft cultures of which recapitulated a robust productive program. While E7 promoted S-phase re-entry in numerous suprabasal differentiated cells, HPV DNA unexpectedly amplified following a prolonged G2 arrest in mid- and upper spinous cells. As viral DNA levels intensified, E7 activity diminished and then extinguished. These cells then exited the cell cycle to undergo virion morphogenesis. High titers of progeny virus generated an indistinguishable productive infection in naïve PHK raft cultures as before, never before achieved until now. An immortalization-defective HPV-18 E6 mutant genome was also characterized for the first time. Numerous cells accumulated p53 protein, without inducing apoptosis, but the productive program was severely curtailed. Complementation of mutant genomes by E6-expressing retrovirus restored proper degradation of p53 as well as viral DNA amplification and L1 production. This system will be invaluable for HPV genetic dissection and serves as a faithful ex vivo model for investigating infections and interventions.

Indexed as

ApoptosisCell Culture TechniquesCells, CulturedDNA-Binding ProteinsDNA ReplicationEpitheliumG2 PhaseGenome, ViralHuman papillomavirus 18HumansKeratinocytesMicroscopy, Electron, TransmissionOncogene Proteins, ViralPapillomavirus InfectionsPlasmidsTime FactorsDNA-Binding ProteinsE7 protein, Human papillomavirus type 18Oncogene Proteins, ViralTumor Suppressor Protein p53

Identifiers

PMID19131434
PMCPMC2648537

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.