Evidence map›Paper›PMID 36757924›Full record

ArticlePLoS biology2023

Fibroblast-expressed LRRC15 is a receptor for SARS-CoV-2 spike and controls antiviral and antifibrotic transcriptional programs.

Lipin Loo, Matthew A Waller, Cesar L Moreno, Alexander J Cole, Alberto Ospina Stella, Oltin-Tiberiu Pop, Ann-Kristin Jochum, Omar Hasan Ali, Christopher E Denes, Zina Hamoudi and 13 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

24 citing papers in PubMed, 33 citations in OpenAlex.

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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

23 authors at 5 institutions in 4 countries.

Lipin LooCharles Perkins Centre, Dr. John and Anne Chong Lab for Functional Genomics, Centenary Institute, and School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Matthew A WallerCharles Perkins Centre, Dr. John and Anne Chong Lab for Functional Genomics, Centenary Institute, and School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Cesar L MorenoCharles Perkins Centre, Dr. John and Anne Chong Lab for Functional Genomics, Centenary Institute, and School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Alexander J ColeCentenary Institute and Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Alberto Ospina StellaThe Kirby Institute, University of New South Wales, New South Wales, Australia.
Oltin-Tiberiu PopInstitute for Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Ann-Kristin JochumInstitute for Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Omar Hasan AliInstitute for Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Christopher E DenesCharles Perkins Centre, Dr. John and Anne Chong Lab for Functional Genomics, Centenary Institute, and School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Zina HamoudiCharles Perkins Centre, Dr. John and Anne Chong Lab for Functional Genomics, Centenary Institute, and School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Felicity ChungCharles Perkins Centre, Dr. John and Anne Chong Lab for Functional Genomics, Centenary Institute, and School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.
Anupriya AggarwalThe Kirby Institute, University of New South Wales, New South Wales, Australia.
Jason K K LowSchool of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Karishma PatelSchool of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Rezwan SiddiqueeSchool of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Taeyoung KangDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Suresh MathivananDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia.
Joel P MackaySchool of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Wolfram JochumInstitute for Pathology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Lukas FlatzInstitute for Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Daniel HesselsonCentenary Institute and Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Stuart TurvilleThe Kirby Institute, University of New South Wales, New South Wales, Australia.
G Gregory NeelyCharles Perkins Centre, Dr. John and Anne Chong Lab for Functional Genomics, Centenary Institute, and School of Life and Environmental Sciences, University of Sydney, Camperdown, New South Wales, Australia.ORCID 0000-0002-1957-9732
The University of Sydney · AUKantonsspital St. Gallen · CHUNSW Sydney · AULa Trobe University · AUUniversity of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although ACE2 is the primary receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, a systematic assessment of host factors that regulate binding to SARS-CoV-2 spike protein has not been described. Here, we use whole-genome CRISPR activation to identify host factors controlling cellular interactions with SARS-CoV-2. Our top hit was a TLR-related cell surface receptor called leucine-rich repeat-containing protein 15 (LRRC15). LRRC15 expression was sufficient to promote SARS-CoV-2 spike binding where they form a cell surface complex. LRRC15 mRNA is expressed in human collagen-producing lung myofibroblasts and LRRC15 protein is induced in severe Coronavirus Disease 2019 (COVID-19) infection where it can be found lining the airways. Mechanistically, LRRC15 does not itself support SARS-CoV-2 infection, but fibroblasts expressing LRRC15 can suppress both pseudotyped and authentic SARS-CoV-2 infection in trans. Moreover, LRRC15 expression in fibroblasts suppresses collagen production and promotes expression of IFIT, OAS, and MX-family antiviral factors. Overall, LRRC15 is a novel SARS-CoV-2 spike-binding receptor that can help control viral load and regulate antiviral and antifibrotic transcriptional programs in the context of COVID-19 infection.

Indexed as

COVID-19SARS-CoV-2Angiotensin-Converting Enzyme 2Antiviral AgentsFibroblastsHumansMembrane ProteinsProtein BindingSpike Glycoprotein, CoronavirusAngiotensin-Converting Enzyme 2Antiviral AgentsLRRC15 protein, humanMembrane ProteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID36757924
PMCPMC9910744
OpenAlexW4319655799

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.