Evidence map›Paper›PMID 32235678›Full record

ArticleCells2020

Hepatitis B Virus HBx Protein Mediates the Degradation of Host Restriction Factors through the Cullin 4 DDB1 E3 Ubiquitin Ligase Complex.

Marissa M Minor, F Blaine Hollinger, Adrienne L McNees, Sung Yun Jung, Antrix Jain, Joseph M Hyser, Karl-Dimiter Bissig, Betty L Slagle

Open access · goldAbstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

31 citing papers in PubMed, 32 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

8 authors at 1 institution in 1 country.

Marissa M MinorDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
F Blaine HollingerDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Adrienne L McNeesDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Sung Yun JungDan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Antrix JainMass Spectrometry Proteomics Core, Baylor College of Medicine, Houston, TX 77030, USA.
Joseph M HyserDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Karl-Dimiter BissigCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Betty L SlagleDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Baylor College of Medicine · US

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9M
Hepatitis HBx-Mediated PathogenesisR01CA095388 · NCI · BAYLOR COLLEGE OF MEDICINE · PI SLAGLE, BETTY L · 2003 to 2007
$1.5M
Hepatitis B virus replication and DDB1R21CA177951 · NCI · BAYLOR COLLEGE OF MEDICINE · PI SLAGLE, BETTY L · 2013 to 2014
$369k
NCI NIH HHS P30 CA125123NIH HHS R01CA095388NIH HHS R21CA177951
6 · The paper itself

Abstract

The hepatitis B virus (HBV) regulatory HBx protein is required for infection, and its binding to cellular damaged DNA binding protein 1 (DDB1) is critical for this function. DDB1 is an adaptor protein for the cullin 4A Really Interesting New Gene (RING) E3 ubiquitin ligase (CRL4) complex and functions by binding cellular DDB1 cullin associated factor (DCAF) receptor proteins that recruit substrates for ubiquitination and degradation. We compared the proteins found in the CRL4 complex immunoprecipitated from uninfected versus HBV-infected hepatocytes from human liver chimeric mice for insight into mechanisms by which HBV and the cell interact within the CRL4 complex. Consistent with its role as a viral DCAF, HBx was found in the HBV CRL4 complexes. In tissue culture transfection experiments, we showed that HBx expression led to decreased levels of known restriction factor structural maintenance of chromosomes protein 6 (SMC6) and putative restriction factors stromal interaction molecule 1 (STIM1, zinc finger E-box binding homeobox 2 (ZEB2), and proteasome activator subunit 4 (PSME4). Moreover, silencing of these proteins led to increased HBV replication in the HepG2-sodium taurocholate cotransporting polypeptide (NTCP) infection model. We also identified cellular DCAF receptors in CRL4 complexes from humanized mice. Increasing amounts of HBx did not reveal competitive DCAF binding to cullin4 (CUL4)-DDB1 in plasmid-transfected cells. Our results suggest a model in which HBx benefits virus replication by directly or indirectly degrading multiple cellular restriction factors.

Indexed as

Host-Pathogen InteractionsDNA-Binding ProteinsHEK293 CellsHepatitis B virusHep G2 CellsHumansLiverModels, BiologicalMultiprotein ComplexesProtein BindingTrans-ActivatorsViral Regulatory and Accessory ProteinsVirus ReplicationDDB1 protein, humanDNA-Binding Proteinshepatitis B virus X proteinMultiprotein ComplexesTrans-ActivatorsViral Regulatory and Accessory Proteinscullin 4 RING E3 ligasedamaged DNA binding protein 1DDB1 cullin accessory factorHBxhepatitis B virusSMC6

Identifiers

PMID32235678
PMCPMC7226812
OpenAlexW3013995821

What OpenQuestion holds

Textmetadata
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.