Evidence map›Paper›PMID 34232859›Full record

ArticleeLife2021

Genetic depletion studies inform receptor usage by virulent hantaviruses in human endothelial cells.

Maria Eugenia Dieterle, Carles Solà-Riera, Chunyan Ye, Samuel M Goodfellow, Eva Mittler, Ezgi Kasikci, Steven B Bradfute, Jonas Klingström, Rohit K Jangra, Kartik Chandran

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.2field-weighted citation impact, top 18% 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

19 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Hantavirus GnACS infectious diseases · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Tropism ofViruses · 2023
    Article
  16. Review
  17. Review
  18. Review
  19. 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

10 authors at 3 institutions in 2 countries.

Maria Eugenia DieterleDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States.ORCID 0000-0002-5257-7253
Carles Solà-RieraCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Chunyan YeUniversity of New Mexico Health Science Center, Center for Global Health, Department of Internal Medicine, Albuquerque, United States.
Samuel M GoodfellowUniversity of New Mexico Health Science Center, Center for Global Health, Department of Internal Medicine, Albuquerque, United States.
Eva MittlerDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States.
Ezgi KasikciDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States.ORCID 0000-0003-4570-3781
Steven B BradfuteUniversity of New Mexico Health Science Center, Center for Global Health, Department of Internal Medicine, Albuquerque, United States.
Jonas KlingströmCenter for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-9076-1441
Rohit K JangraDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States.ORCID 0000-0002-3119-0869
Kartik ChandranDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States.ORCID 0000-0003-0232-7077
Albert Einstein College of Medicine · USUniversity of New Mexico · USKarolinska Institutet · SE

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI THOMAS E ROHAN · 1985 to 2026
$111.2M
Biology of Infectious Diseases &InflammationT32AI007538 · NIAID · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Michelle A Ozbun · 1998 to 2026
$5.2M
Dissecting the receptor-mediated infection mechanisms of hantavirusesR01AI132633 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CHANDRAN, KARTIK · 2017 to 2021
$3.2M
NCI NIH HHS P30 CA013330NIAID NIH HHS R01 AI132633NIAID NIH HHS T32 AI007538Swedish Research Council 2018-02646
6 · The paper itself

Abstract

Hantaviruses are RNA viruses with known epidemic threat and potential for emergence. Several rodent-borne hantaviruses cause zoonoses accompanied by severe illness and death. However, assessments of zoonotic risk and the development of countermeasures are challenged by our limited knowledge of the molecular mechanisms of hantavirus infection, including the identities of cell entry receptors and their roles in influencing viral host range and virulence. Despite the long-standing presumption that β3/β1-containing integrins are the major hantavirus entry receptors, rigorous genetic loss-of-function evidence supporting their requirement, and that of decay-accelerating factor (DAF), is lacking. Here, we used CRISPR/Cas9 engineering to knockout candidate hantavirus receptors, singly and in combination, in a human endothelial cell line that recapitulates the properties of primary microvascular endothelial cells, the major targets of viral infection in humans. The loss of β3 integrin, β1 integrin, and/or DAF had little or no effect on entry by a large panel of hantaviruses. By contrast, loss of protocadherin-1, a recently identified entry receptor for some hantaviruses, substantially reduced hantavirus entry and infection. We conclude that major host molecules necessary for endothelial cell entry by PCDH1-independent hantaviruses remain to be discovered.

Indexed as

Cell LineEndothelial CellsHumansOrthohantavirusReceptors, Cell SurfaceViral ProteinsReceptors, Cell SurfaceViral ProteinsCRISPR/Cas9Endothelial cellsHantavirusinfectious diseasemicrobiologyreceptorvirus

Identifiers

PMID34232859
PMCPMC8263056
OpenAlexW3178377702

What OpenQuestion 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 OpenQuestion graph.