Evidence map›Paper›PMID 41754530›Full record

ArticleViruses2026

Development of a Novel Human Hepatoma Cell Line Supporting the Replication of a Recombinant HBV Genome with a Reporter Gene.

Shotaro Kawase, Tetsuro Shimakami, Kazuyuki Kuroki, Kazuhisa Murai, Masaya Funaki, Mika Yoshita, Masaki Kakuya, Reo Suzuki, Ying-Yi Li, Dolgormaa Gantumur and 7 more

Abstract read
In one paragraph

Article in Viruses, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Article
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

17 authors.

Shotaro KawaseDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.
Tetsuro ShimakamiDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.
Kazuyuki KurokiDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.
Kazuhisa MuraiAdvanced Science Research Center, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Ishikawa, Japan.ORCID 0000-0003-0562-777X
Masaya FunakiDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.ORCID 0000-0001-5936-6371
Mika YoshitaDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.
Masaki KakuyaDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.
Reo SuzukiDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.
Ying-Yi LiDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.ORCID 0000-0002-6269-2992
Dolgormaa GantumurDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.ORCID 0000-0002-0727-2813
Taro KawaneDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.
Koji MatsumoriDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.
Kouki NioDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.ORCID 0000-0002-0971-8313
Kazunori KawaguchiDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.ORCID 0000-0002-4927-1704
Hajime TakatoriDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.
Masao HondaAdvanced Science Research Center, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Ishikawa, Japan.ORCID 0000-0003-3050-5854
Taro YamashitaDepartment of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan.ORCID 0000-0002-3383-9131

Funding

Japan Agency for Medical Research and Development JP24fk0310503; JP25fk0310529; JP24fk0310514; JP25fk0310539Japan Society for the Promotion of Science 23K27581; 23H02890; 24K18968
6 · The paper itself

Abstract

Hepatitis B virus (HBV) remains a major global health threat because covalently closed circular DNA (cccDNA) persists in hepatocytes and limits the efficacy of current antiviral therapies. Effective HBV research and drug screening require culture models that recapitulate the complete viral life cycle and allow for quantitative monitoring of replication. In this study, an 11-amino acid luminescent reporter, HiBiT, was inserted at multiple sites within the preS1 region of a genotype D HBV genome, and the C terminus of preS1 was identified as optimal for maintaining robust replication. We then established HepG2-B4 cells stably replicating HiBiT-HBV with HiBiT at the preS1 C terminus. Extracellular HiBiT activity and supernatant levels of HBV-DNA, HBsAg, and HBcAg increased continuously until day 42 and were reduced by nucleos(t)ide analog treatment, and cccDNA was confirmed by Southern blot analysis. Supernatants from HepG2-B4 cells infected naïve HepG2-NTCP cells and primary human hepatocytes, as shown by extracellular HiBiT activity. Transcriptome analysis revealed distinct gene expression changes in HepG2-B4 cells compared with parental HepG2 cells. These findings indicate that the HepG2-B4 system provides a rapid, quantitative, and scalable platform for HBV replication and infection studies and is suitable for mechanistic investigations and high-throughput antiviral screening.

Indexed as

Genes, ReporterGenome, ViralHepatitis B virusVirus ReplicationCell Line, TumorDNA, CircularDNA, ViralHepatitis B Surface AntigensHepatocytesHep G2 CellsHumansDNA, CircularDNA, ViralHepatitis B Surface Antigensantiviral screeningcovalently closed circular DNA (cccDNA)hepatitis B virus (HBV)HepG2HiBiTNanoLuc® Binary Technology (NanoBiT)

Identifiers

PMID41754530
PMCPMC12944927

What OpenQuestion holds

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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.