Evidence map›Paper›PMID 34363922›Full record

ArticleJournal of hepatology2021

Infection courses, virological features and IFN-α responses of HBV genotypes in cell culture and animal models.

Min Zhang, Zhensheng Zhang, Michio Imamura, Mitsutaka Osawa, Yuji Teraoka, Jason Piotrowski, Yuji Ishida, Vitina Sozzi, Peter A Revill, Takeshi Saito and 2 more

Open access · greenAbstract read
In one paragraph

Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

23 citing papers in PubMed, 33 citations in OpenAlex.

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  15. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022).Journal of clinical and translational hepatology · 2023
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. [Guidelines for the prevention and treatment of chronic hepatitis B (version 2022)].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022
    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

12 authors at 4 institutions in 3 countries.

Min ZhangLiver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA.
Zhensheng ZhangLiver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA.
Michio ImamuraDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
Mitsutaka OsawaDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
Yuji TeraokaDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical & Health Science, Hiroshima University, Hiroshima, Japan.
Jason PiotrowskiLiver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA.
Yuji IshidaDivision of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA; PhoenixBio Co., Ltd., Higashi-Hiroshima, Hiroshima, Japan.
Vitina SozziVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Peter A RevillVictorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Takeshi SaitoDivision of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA.
Kazuaki ChayamaCollaborative Research Laboratory of Medical Innovation, Hiroshima University, Hiroshima, Japan.
T Jake LiangLiver Diseases Branch, NIDDK, NIH, Bethesda, MD, USA. Electronic address: jliang@nih.gov.
Hiroshima University · JPNational Institutes of Health · USThe Royal Melbourne Hospital · AUUniversity of Southern California · US

Funding

Molecular Mechanisms Of Hepatitis B Viral Pathogenesis And PersistenceZIADK054500 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 2009 to 2025
$20.3M
Therapy, Vaccine and Model Development in Viral Hepatitis and Liver DiseasesZIADK054505 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 2009 to 2025
$17.5M
Studies of HCV Infection, Vaccine Development and HCV-Host interactionsZIADK054504 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 2009 to 2022
$12.0M
Natural History, Therapy and Pathogenesis of Chronic Viral Hepatitis BZIADK054517 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI GHANY, MARC · 2009 to 2025
$9.6M
Innate Defense Program against HCVR01DK101773 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SAITO, TAKESHI · 2015 to 2019
$1.9M
TRANSGENIC MOUSE MODEL FOR STUDY OF VIRAL HEPATITIS CZ01DK054504 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 1997 to 2008
$1.0M
MOLECULAR MECHANISMS OF HEPATITIS B VIRAL PATHOGENESIS AND PERSISTENCEZ01DK054500 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 1997 to 2008
$927k
Natural History, Therapy and Pathogenesis of Chronic Viral Hepatitis BZ01DK054517 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI GHANY, MARC · 2008 to 2008
$567k
Impact of Occult Hepatitis C Virus Infection in Progression of Liver DiseasesR21AI139954 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SAITO, TAKESHI · 2018 to 2019
$454k
Intramural NIH HHS Z01 DK054500Intramural NIH HHS Z01 DK054504Intramural NIH HHS Z01 DK054517Intramural NIH HHS Z99 DK999999Intramural NIH HHS ZIA DK054500Intramural NIH HHS ZIA DK054505NIAID NIH HHS R21 AI139954NIDDK NIH HHS R01 DK101773
6 · The paper itself

Abstract

BACKGROUND &

aimsHBV consists of 9 major genotypes (A to I), 1 minor strain (designated J) and multiple subtypes, which may be associated with different clinical characteristics. As only cell lines expressing genotype D3 have been established, herein, we aimed to establish stable cell lines producing high-titer cell culture-generated HBV (HBVcc) of different genotypes and to explore their infectivity, virological features and responses to treatment.

methodsStable cell lines producing high titers of HBV genotype A2, B2, C1, E, F1b and H were generated by transfecting plasmids containing a replication-competent 1.3x length HBV genome and an antibiotic marker into HepG2 cells that can support HBV replication. Clones with the highest levels of HBV DNA and/or HBeAg were selected and expanded for large-scale purification of HBVcc. HBVcc of different genotypes were tested in cells and a humanized chimeric mouse model.

resultsHBVcc genotypes were infectious in mouse-passaged primary human hepatocytes (PXB cells) and responded differently to human interferon (IFN)-α with variable kinetics of reduction in HBV DNA, HBeAg and HBsAg. HBVcc of all genotypes were infectious in humanized chimeric mice but with variable kinetics of viremia and viral antigen production. Treatment of infected mice with human IFN-α resulted in modest and variable reductions of viremia and viral antigenemia. HBVcc passaged in humanized chimeric mice (HBVmp) infected PXB cells much more efficiently than that of the original HBVcc viral stock.

conclusionsHerein, we generated stable cell lines producing HBV of various genotypes that are infectious in vitro and in vivo. We observe genotype-associated variations in viral antigen production, infection kinetics and responses to human IFN-α treatment in these models. LAY SUMMARY: Stable cell lines producing high-titer cell culture-generated hepatitis B virus (HBV) of various genotypes were established. HBV genotypes showed stable infectivity in both in vitro and in vivo models, which are valuable tools for antiviral development.

Indexed as

GenotypeAnimalsCell Culture TechniquesDisease Models, AnimalHepatitis BHepatitis B virusMiceinfection modelliver diseasestable cell linestreatmentVirus genotypes

Identifiers

PMID34363922
PMCPMC8604785
OpenAlexW3187144661

What OpenQuestion holds

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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.