Evidence map›Paper›PMID 32799415›Full record

ArticleCellular microbiology2020

Synchronised infection identifies early rate-limiting steps in the hepatitis B virus life cycle.

Anindita Chakraborty, Chunkyu Ko, Christin Henning, Aaron Lucko, James M Harris, Fuwang Chen, Xiaodong Zhuang, Jochen M Wettengel, Stephanie Roessler, Ulrike Protzer and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Cellular microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.3field-weighted citation impact, top 10% 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

21 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Hepatitis B Virus Neutralization with DNA Origami Nanoshells.ACS applied materials & interfaces · 2024
    Article
  7. Article
  8. The Culprit Behind HBV-Infected Hepatocytes: NTCP.Drug design, development and therapy · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Concentration of NaScientific reports · 2021
    Article
  18. Article
  19. Article
  20. Review
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

11 authors at 3 institutions in 2 countries.

Anindita ChakrabortyInstitute of Virology, Technical University of Munich, School of Medicine/Helmholtz Zentrum München, Munich, Germany.
Chunkyu KoInstitute of Virology, Technical University of Munich, School of Medicine/Helmholtz Zentrum München, Munich, Germany.
Christin HenningInstitute of Virology, Technical University of Munich, School of Medicine/Helmholtz Zentrum München, Munich, Germany.ORCID 0000-0001-8061-2821
Aaron LuckoInstitute of Virology, Technical University of Munich, School of Medicine/Helmholtz Zentrum München, Munich, Germany.
James M HarrisNuffield Department of Medicine, University of Oxford, Oxford, UK.
Fuwang ChenInstitute of Virology, Technical University of Munich, School of Medicine/Helmholtz Zentrum München, Munich, Germany.
Xiaodong ZhuangNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0002-6870-9003
Jochen M WettengelInstitute of Virology, Technical University of Munich, School of Medicine/Helmholtz Zentrum München, Munich, Germany.
Stephanie RoesslerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Ulrike ProtzerInstitute of Virology, Technical University of Munich, School of Medicine/Helmholtz Zentrum München, Munich, Germany.
Jane A McKeatingNuffield Department of Medicine, University of Oxford, Oxford, UK.ORCID 0000-0002-7229-5886
Helmholtz Zentrum München · DEUniversity of Oxford · GBHeidelberg University · DE

Funding

Medical Research Council G0400802Medical Research Council G0801976Medical Research Council G1100247Medical Research Council MR/R022011/1Wellcome Trust 200838Wellcome Trust IA 200838/Z/16/Z
6 · The paper itself

Abstract

Hepatitis B virus (HBV) is an enveloped DNA virus that contains a partially double-stranded relaxed circular (rc) DNA. Upon infection, rcDNA is delivered to the nucleus where it is repaired to covalently closed circular (ccc) DNA that serves as the transcription template for all viral RNAs. Our understanding of HBV particle entry dynamics and host pathways regulating intracellular virus trafficking and cccDNA formation is limited. The discovery of sodium taurocholate co-transporting peptide (NTCP) as the primary receptor allows studies on these early steps in viral life cycle. We employed a synchronised infection protocol to quantify HBV entry kinetics. HBV attachment to cells at 4°C is independent of NTCP, however, subsequent particle uptake is NTCP-dependent and reaches saturation at 12 h post-infection. HBV uptake is clathrin- and dynamin dependent with actin and tubulin playing a role in the first 6 h of infection. Cellular fractionation studies demonstrate HBV DNA in the nucleus within 6 h of infection and cccDNA was first detected at 24 h post-infection. Our studies show the majority (83%) of cell bound particles enter HepG2-NTCP cells, however, only a minority (<1%) of intracellular rcDNA was converted to cccDNA, highlighting this as a rate-limiting in establishing infection in vitro. This knowledge highlights the deficiencies in our in vitro cell culture systems and will inform the design and evaluation of physiologically relevant models that support efficient HBV replication.

Indexed as

Virus ReplicationDNA, ViralHepatitis B virusHepatocytesHep G2 CellsHumansIn Vitro TechniquesKineticsLife Cycle StagesRNA, ViralSymportersVirus InternalizationDNA, ViralRNA, ViralSymportershepatitis Bkineticsvirus internalisation

Identifiers

PMID32799415
PMCPMC7611726
OpenAlexW3047608690

What Socratic 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 Socratic graph.