Evidence map›Paper›PMID 33384338›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46.

B David Persson, Lijo John, Karim Rafie, Michael Strebl, Lars Frängsmyr, Monika Z Ballmann, Katja Mindler, Menzo Havenga, Angelique Lemckert, Thilo Stehle and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
7.9field-weighted citation impact, top 2% 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

46 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Medical Gas Plasma Inactivates Adenoviruses via Capsid Oxidation.Small (Weinheim an der Bergstrasse, Germany) · 2026
    Article
  5. Article
  6. Article
  7. The multiverse of CD46 and oncologic interactions.The Journal of clinical investigation · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
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  15. Article
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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

12 authors at 3 institutions in 3 countries.

B David PerssonDepartment of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden.
Lijo JohnDepartment of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden.ORCID https://orcid.org/0000-0002-5459-5359
Karim RafieLaboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.ORCID https://orcid.org/0000-0003-2418-0061
Michael StreblInterfaculty Institute of Biochemistry, The University of Tübingen, D-72076 Tübingen, Germany.ORCID https://orcid.org/0000-0001-9287-5549
Lars FrängsmyrDepartment of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden.
Monika Z BallmannBatavia Biosciences, 2333 CL Leiden, The Netherlands.
Katja MindlerInterfaculty Institute of Biochemistry, The University of Tübingen, D-72076 Tübingen, Germany.ORCID https://orcid.org/0000-0002-6730-4151
Menzo HavengaBatavia Biosciences, 2333 CL Leiden, The Netherlands.ORCID https://orcid.org/0000-0003-4094-6362
Angelique LemckertBatavia Biosciences, 2333 CL Leiden, The Netherlands.ORCID https://orcid.org/0000-0003-0151-0953
Thilo StehleInterfaculty Institute of Biochemistry, The University of Tübingen, D-72076 Tübingen, Germany.
Lars-Anders CarlsonLaboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.ORCID https://orcid.org/0000-0003-2342-6488
Niklas ArnbergDepartment of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden; niklas.arnberg@umu.se.ORCID https://orcid.org/0000-0002-7069-6678
Umeå University · SEBatavia Biosciences (Netherlands) · NLUniversity of Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human adenovirus species D (HAdV-D) types are currently being explored as vaccine vectors for coronavirus disease 2019 (COVID-19) and other severe infectious diseases. The efficacy of such vector-based vaccines depends on functional interactions with receptors on host cells. Adenoviruses of different species are assumed to enter host cells mainly by interactions between the knob domain of the protruding fiber capsid protein and cellular receptors. Using a cell-based receptor-screening assay, we identified CD46 as a receptor for HAdV-D56. The function of CD46 was validated in infection experiments using cells lacking and overexpressing CD46, and by competition infection experiments using soluble CD46. Remarkably, unlike HAdV-B types that engage CD46 through interactions with the knob domain of the fiber protein, HAdV-D types infect host cells through a direct interaction between CD46 and the hexon protein. Soluble hexon proteins (but not fiber knob) inhibited HAdV-D56 infection, and surface plasmon analyses demonstrated that CD46 binds to HAdV-D hexon (but not fiber knob) proteins. Cryoelectron microscopy analysis of the HAdV-D56 virion-CD46 complex confirmed the interaction and showed that CD46 binds to the central cavity of hexon trimers. Finally, soluble CD46 inhibited infection by 16 out of 17 investigated HAdV-D types, suggesting that CD46 is an important receptor for a large group of adenoviruses. In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors.

Indexed as

Adenoviruses, HumanCapsid ProteinsCOVID-19 VaccinesGene Expression Regulation, ViralVirus InternalizationCell LineHumansSARS-CoV-2Capsid ProteinsCOVID-19 VaccinesadenovirusCD46hexonreceptorvaccine

Identifiers

PMID33384338
PMCPMC7826407
OpenAlexW3115163609

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.