Evidence map›Paper›PMID 39316623›Full record

ArticlePLoS biology2024

A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist.

Jérémie Le Pen, Gabrielle Paniccia, Volker Kinast, Marcela Moncada-Velez, Alison W Ashbrook, Michael Bauer, H-Heinrich Hoffmann, Ana Pinharanda, Inna Ricardo-Lax, Ansgar F Stenzel and 29 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Plscr1 inhibits murine norovirus entry.bioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. IFN-inducible human phospholipid scramblase 1 (PLSCR1) protein restricts HIV-1 infection by inhibiting membrane fusion.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Phospholipid scramblase 1: a frontline defense against viral infections.Frontiers in cellular and infection microbiology · 2025
    Review
  14. 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

39 authors.

Jérémie Le PenLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.ORCID 0000-0001-7025-9526
Gabrielle PanicciaLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Volker KinastDepartment of Medical Microbiology and Virology, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
Marcela Moncada-VelezSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, United States of America.
Alison W AshbrookLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Michael BauerLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
H-Heinrich HoffmannLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Ana PinharandaDepartment of Biological Sciences, Columbia University, New York, New York, United States of America.
Inna Ricardo-LaxLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Ansgar F StenzelLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Edwin A Rosado-OlivieriLaboratory of Synthetic Embryology, The Rockefeller University, New York, New York, United States of America.
Kenneth H DinnonLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
William C DoyleLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Catherine A FreijeLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Seon-Hui HongLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Danyel LeeSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, United States of America.
Tyler LewyLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Joseph M LunaLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Avery PeaceLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Carltin SchmidtSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, United States of America.
William M SchneiderLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Roni WinklerLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Elaine Z YipLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Chloe LarsonFisher Drug Discovery Resource Center, The Rockefeller University, New York, New York, United States of America.
Timothy McGinnFisher Drug Discovery Resource Center, The Rockefeller University, New York, New York, United States of America.
Miriam-Rose MenezesFisher Drug Discovery Resource Center, The Rockefeller University, New York, New York, United States of America.
Lavoisier Ramos-EspirituFisher Drug Discovery Resource Center, The Rockefeller University, New York, New York, United States of America.
Priyam BanerjeeBio-Imaging Resource Center, The Rockefeller University, New York, New York, United States of America.
John T PoirierLaura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, New York, United States of America.
Francisco J Sànchez-RiveraDepartment of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Aurélie CobatSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, United States of America.
Qian ZhangSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, United States of America.
Jean-Laurent CasanovaSt Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, United States of America.
Thomas S CarrollBioinformatics Resource Center, The Rockefeller University, New York, New York, United States of America.
J Fraser GlickmanFisher Drug Discovery Resource Center, The Rockefeller University, New York, New York, United States of America.
Eleftherios MichailidisLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Brandon RazookyLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Margaret R MacDonaldLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Charles M RiceLaboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.

Funding

Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6M
Understanding B cell memory in response to diverse virus infectionsU19AI111825 · NIAID · ROCKEFELLER UNIVERSITY · PI RAVETCH, JEFFREY VICTOR · 2014 to 2023
$26.0M
Type I interferon-stimulated genes and the antiviral immune responseR01AI091707 · NIAID · ROCKEFELLER UNIVERSITY · PI RICE, CHARLES M · 2011 to 2020
$5.5M
Inborn errors of immunity in patients with life-threatening COVID-19R01AI163029 · NIAID · ROCKEFELLER UNIVERSITY · PI CASANOVA, JEAN-LAURENT, ZHANG, QIAN · 2021 to 2025
$3.7M
Tracking SARS-CoV-2 one molecule at a time: Spatiotemporal investigation of coronavirus replication dynamics and host response in single cells in vitro and in vivoR01AI161444 · NIAID · ROCKEFELLER UNIVERSITY · PI Charles M Rice · 2022 to 2026
$3.1M
NCATS NIH HHS UL1 TR001866NIAID NIH HHS R01 AI091707NIAID NIH HHS R01 AI161444NIAID NIH HHS R01 AI163029NIAID NIH HHS U19 AI111825
6 · The paper itself

Abstract

Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of Coronavirus Disease 2019 (COVID-19) patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 overexpression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Finally, we investigate the functional effects of PLSCR1 variants present in humans and discuss an association between PLSCR1 and severe COVID-19 reported recently.

Indexed as

COVID-19SARS-CoV-2Virus InternalizationAntigens, DifferentiationClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsHEK293 CellsHumansInterferonsSerine EndopeptidasesSpike Glycoprotein, CoronavirusAntigens, DifferentiationInterferonsleu-13 antigenSerine EndopeptidasesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2TMPRSS2 protein, human

Identifiers

PMID39316623
PMCPMC11486371

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Registered trials

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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.