Evidence map›Paper›PMID 37054914›Full record

ArticleCellular and molecular gastroenterology and hepatology2023

Hepatitis B Virus Targets Lipid Transport Pathways to Infect Hepatocytes.

Knud Esser, Xiaoming Cheng, Jochen M Wettengel, Julie Lucifora, Lea Hansen-Palmus, Katharina Austen, Armando A Roca Suarez, Sarah Heintz, Barbara Testoni, Firat Nebioglu and 18 more

Open access · goldAbstract read
In one paragraph

Article in Cellular and molecular gastroenterology and hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

16 citing papers in PubMed, 21 citations in OpenAlex.

  1. Liver Macrophages in the Pathogenesis of Viral Hepatitis.Current issues in molecular biology · 2026
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  16. Reverse Cholesterol Transport of Macrophages Repurposed for Hepatitis B Virus Entry.Cellular and molecular gastroenterology and hepatology · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 8 institutions in 2 countries.

Knud EsserInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany. Electronic address: knud.esser@tum.de.
Xiaoming ChengInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany.
Jochen M WettengelInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany.
Julie LuciforaINSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, and University of Lyon, Université Claude-Bernard (UCBL), Lyon, France; CIRI-Centre International de Recherche en Infectiologie, Inserm, U1111, University of Lyon, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS Lyon, France.
Lea Hansen-PalmusInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany.
Katharina AustenInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany.
Armando A Roca SuarezCIRI-Centre International de Recherche en Infectiologie, Inserm, U1111, University of Lyon, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS Lyon, France.
Sarah HeintzCIRI-Centre International de Recherche en Infectiologie, Inserm, U1111, University of Lyon, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS Lyon, France.
Barbara TestoniCIRI-Centre International de Recherche en Infectiologie, Inserm, U1111, University of Lyon, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS Lyon, France.
Firat NebiogluHeidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Diseases Research, Heidelberg, Germany.
Minh Tu PhamHeidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Diseases Research, Heidelberg, Germany.
Shangqing YangHeidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Diseases Research, Heidelberg, Germany.
Alma ZerneckeInstitute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany.
Dirk WohlleberInstitute of Molecular Immunology and Experimental Oncology, University Hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany; German Center for Infection Research (DZIF), Munich and Heidelberg partner sites, Munich and Heidelberg, Germany.
Marc RingelhanGerman Center for Infection Research (DZIF), Munich and Heidelberg partner sites, Munich and Heidelberg, Germany; 2nd Medical Department, University Hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany.
Mathias BroxtermannInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany.
Daniel HartmannDepartment of Surgery, University Hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany.
Norbert HüserDepartment of Surgery, University Hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany.
Julia MergnerBavarian Center for Biomolecular Mass Spectrometry at Klinikum rechts der Isar (BayBioMS@MRI), TUM, Munich, Germany.
Andreas PichlmairInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany; German Center for Infection Research (DZIF), Munich and Heidelberg partner sites, Munich and Heidelberg, Germany; Bavarian Center for Biomolecular Mass Spectrometry at Klinikum rechts der Isar (BayBioMS@MRI), TUM, Munich, Germany.
Wolfgang E ThaslerDepartment of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich, Germany.
Mathias HeikenwalderInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany.
Georg GasteigerInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany.
Andreas BlutkeInstitute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
Axel WalchInstitute of Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
Percy A KnolleInstitute of Molecular Immunology and Experimental Oncology, University Hospital rechts der Isar, Technical University of Munich, School of Medicine, Munich, Germany; German Center for Infection Research (DZIF), Munich and Heidelberg partner sites, Munich and Heidelberg, Germany.
Ralf BartenschlagerHeidelberg University, Medical Faculty Heidelberg, Department of Infectious Diseases, Molecular Virology, Center for Integrative Infectious Diseases Research, Heidelberg, Germany; German Center for Infection Research (DZIF), Munich and Heidelberg partner sites, Munich and Heidelberg, Germany; Division Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Ulrike ProtzerInstitute of Virology, Technical University of Munich, School of Medicine / Helmholtz Munich, Munich, Germany; German Center for Infection Research (DZIF), Munich and Heidelberg partner sites, Munich and Heidelberg, Germany. Electronic address: protzer@tum.de.
Helmholtz Zentrum München · DEHeidelberg University · DETUM Klinikum · DEUniversité Claude Bernard Lyon 1 · FRGerman Cancer Research Center · DEGerman Center for Infection Research · DELudwig-Maximilians-Universität München · DEUniversitätsklinikum Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsA single hepatitis B virus (HBV) particle is sufficient to establish chronic infection of the liver after intravenous injection, suggesting that the virus targets hepatocytes via a highly efficient transport pathway. We therefore investigated whether HBV uses a physiological liver-directed pathway that supports specific host-cell targeting in vivo.

methodsWe established the ex vivo perfusion of intact human liver tissue that recapitulates the liver physiology to investigate HBV liver targeting. This model allowed us to investigate virus-host cell interactions in a cellular microenvironment mimicking the in vivo situation.

resultsHBV was rapidly sequestered by liver macrophages within 1 hour after a virus pulse perfusion but was detected in hepatocytes only after 16 hours. We found that HBV associates with lipoproteins in serum and within machrophages. Electron and immunofluorescence microscopy corroborated a co-localization in recycling endosomes within peripheral and liver macrophages. Recycling endosomes accumulated HBV and cholesterol, followed by transport of HBV back to the cell surface along the cholesterol efflux pathway. To reach hepatocytes as final target cells, HBV was able to utilize the hepatocyte-directed cholesterol transport machinery of macrophages.

conclusionsOur results propose that by binding to liver targeted lipoproteins and using the reverse cholesterol transport pathway of macrophages, HBV hijacks the physiological lipid transport pathways to the liver to most efficiently reach its target organ. This may involve transinfection of liver macrophages and result in deposition of HBV in the perisinusoidal space from where HBV can bind its receptor on hepatocytes.

Indexed as

Hepatitis BHepatitis B virusCholesterolHepatocytesHumansLipidsLipoproteinsCholesterolLipidsLipoproteinsLipoprotein MetabolismLiver TargetingTranscytosisTransinfection

Identifiers

PMID37054914
PMCPMC10394270
OpenAlexW4364378762

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.