Evidence map›Paper›PMID 29494681›Full record

ArticlePLoS pathogens2018

A new cell culture model to genetically dissect the complete human papillomavirus life cycle.

Malgorzata Bienkowska-Haba, Wioleta Luszczek, Julia E Myers, Timothy R Keiffer, Stephen DiGiuseppe, Paula Polk, Jason M Bodily, Rona S Scott, Martin Sapp

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
4.9field-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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

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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

9 authors at 1 institution in 1 country.

Malgorzata Bienkowska-HabaDepartment of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.ORCID 0000-0002-9669-1875
Wioleta LuszczekDepartment of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
Julia E MyersDepartment of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.ORCID 0000-0002-5371-8361
Timothy R KeifferDepartment of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.ORCID 0000-0001-7104-6338
Stephen DiGiuseppeDepartment of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.ORCID 0000-0002-9925-9850
Paula PolkResearch Core Facility, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
Jason M BodilyDepartment of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.ORCID 0000-0001-9743-2085
Rona S ScottDepartment of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.ORCID 0000-0003-3840-9189
Martin SappDepartment of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.ORCID 0000-0003-3916-8890
Louisiana State University Health Sciences Center Shreveport · US

Funding

COBRE Center for Molecular and Tumor VirologyP30GM110703 · NIGMS · LOUISIANA STATE UNIV HSC SHREVEPORT · PI SAPP, MARTIN · 2014 to 2018
$4.8M
Immediate early events of the HPV life cycleR01CA211576 · NCI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI Katarzyna Zwolinska · 2017 to 2026
$2.8M
Epigenetic Effects of Epstein-Barr Virus Infection in Oral Squamous Cell CarcinomaR01DE025565 · NIDCR · LOUISIANA STATE UNIV HSC SHREVEPORT · PI SCOTT, RONA S · 2015 to 2019
$1.8M
Cell surface events of human papillomavirus type 16 and 18 infectionR01AI081809 · NIAID · LOUISIANA STATE UNIV HSC SHREVEPORT · PI SAPP, MARTIN · 2009 to 2013
$1.8M
ThThe Role of Epithelial-Stromal Communication in the Human Papillomavirus Type 16 Life CycleR01AI118904 · NIAID · LOUISIANA STATE UNIV HSC SHREVEPORT · PI BODILY, JASON M · 2015 to 2019
$1.6M
NCI NIH HHS R01 CA211576NIAID NIH HHS R01 AI081809NIAID NIH HHS R01 AI118904NIDCR NIH HHS R01 DE025565NIGMS NIH HHS P30 GM110703NIH HHS R01AI081809NIH HHS R01CA211576
6 · The paper itself

Abstract

Herein, we describe a novel infection model that achieves highly efficient infection of primary keratinocytes with human papillomavirus type 16 (HPV16). This cell culture model does not depend on immortalization and is amenable to extensive genetic analyses. In monolayer cell culture, the early but not late promoter was active and yielded a spliced viral transcript pattern similar to HPV16-immortalized keratinocytes. However, relative levels of the E8^E2 transcript increased over time post infection suggesting the expression of this viral repressor is regulated independently of other early proteins and that it may be important for the shift from the establishment to the maintenance phase of the viral life cycle. Both the early and the late promoter were strongly activated when infected cells were subjected to differentiation by growth in methylcellulose. When grown as organotypic raft cultures, HPV16-infected cells expressed late E1^E4 and L1 proteins and replication foci were detected, suggesting that they supported the completion of the viral life cycle. As a proof of principle that the infection system may be used for genetic dissection of viral factors, we analyzed E1, E6 and E7 translation termination linker mutant virus for establishment of infection and genome maintenance. E1 but not E6 and E7 was essential to establish infection. Furthermore, E6 but not E7 was required for episomal genome maintenance. Primary keratinocytes infected with wild type HPV16 immortalized, whereas keratinocytes infected with E6 and E7 knockout virus began to senesce 25 to 35 days post infection. The novel infection model provides a powerful genetic tool to study the role of viral proteins throughout the viral life cycle but especially for immediate early events and enables us to compare low- and high-risk HPV types in the context of infection.

Indexed as

Gene Expression Regulation, ViralVirus ReplicationCells, CulturedHuman papillomavirus 16HumansKeratinocytesOncogene Proteins, ViralPapillomavirus InfectionsOncogene Proteins, Viral

Identifiers

PMID29494681
PMCPMC5833277
OpenAlexW2794336305

What OpenQuestion holds

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LicenceCC BY
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.