Evidence map›Paper›PMID 34749533›Full record

ArticlemBio2021

Spatial and Functional Organization of Human Papillomavirus Replication Foci in the Productive Stage of Infection.

Simran Khurana, Tovah E Markowitz, Juraj Kabat, Alison A McBride

Open access · goldAbstract read
In one paragraph

Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
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  10. Histone H2A variants: Diversifying chromatin to ensure genome integrity.Seminars in cell & developmental biology · 2023
    Review
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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

4 authors at 1 institution in 1 country.

Simran KhuranaLaboratory of Viral Diseases, National Institute of Allergy and Infectious Diseasesgrid.419681.3, National Institutes of Health, Bethesda, Maryland, USA.
Tovah E MarkowitzNIAID Collaborative Bioinformatics Resource (NCBR), National Institute of Allergy and Infectious Diseasesgrid.419681.3, National Institutes of Health, Bethesda, Maryland, USA.
Juraj KabatBiological Imaging Section, National Institute of Allergy and Infectious Diseasesgrid.419681.3, National Institutes of Health, Bethesda, Maryland, USA.
Alison A McBrideLaboratory of Viral Diseases, National Institute of Allergy and Infectious Diseasesgrid.419681.3, National Institutes of Health, Bethesda, Maryland, USA.ORCID 0000-0001-5607-5157
National Institutes of Health · US

Funding

Replication mechanisms of human papillomaviruses (HPV)ZIAAI000713 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MCBRIDE, ALISON · 2009 to 2025
$12.4M
Characterization: Papillomavirus Regulatory ProteinsZ01AI000713 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI MCBRIDE, ALISON · 1994 to 2008
$1.4M
Intramural NIH HHS Z01 AI000713Intramural NIH HHS ZIA AI000713
6 · The paper itself

Abstract

The life cycle of human papillomavirus (HPV) depends on keratinocyte differentiation as the virus modulates and takes advantage of cellular pathways to replicate its genome and assemble viral particles in differentiated cells. Viral genomes are amplified in nuclear replication foci in differentiated keratinocytes, and DNA repair factors from the DNA damage response signaling pathway are recruited to replicate viral DNA. The HPV genome is associated with cellular histones at all stages of the infectious cycle, and here, we show that the histone variant macroH2A1 is bound to the HPV genome and enriched in viral replication foci in differentiated cells. macroH2A1 isoforms play important roles in cellular transcriptional repression, double-strand break repair, and replication stress. The viral E8^E2 protein also binds to the HPV genome and inhibits viral replication and gene expression by recruiting NCoR/SMRT complexes. We show here that E8^E2 and SMRT also localize within replication foci, though independently from macroH2A1. Conversely, transcription complexes containing RNA polymerase II and Brd4 are located on the surface of the foci. Foci generated with an HPV16 E8^E2 mutant genome are not enriched for SMRT or macroH2A1 but contain transcriptional complexes throughout the foci. We propose that both the cellular macroH2A1 protein and viral E8^E2 protein help to spatially separate replication and transcription activities within viral replication foci.

Indexed as

Genome, ViralVirus ReplicationAlphapapillomavirusHistonesHost-Pathogen InteractionsHumansNuclear Receptor Co-Repressor 1Nuclear Receptor Co-Repressor 2Oncogene Proteins, ViralPapillomavirus InfectionsHistonesMACROH2A1 protein, humanNCOR1 protein, humanNCOR2 protein, humanNuclear Receptor Co-Repressor 1Nuclear Receptor Co-Repressor 2Oncogene Proteins, ViralchromatinDNA replicationepigeneticshistone variant macroH2A1HPVhuman papillomaviruskeratinocytespapillomavirustranscriptionviral replicationvirus-host interactions

Identifiers

PMID34749533
PMCPMC8576538
OpenAlexW3211943633

What Socratic 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 Socratic graph.