In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 2 ( 2023-2-9), p. e3001967-
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001967
DOI:
10.1371/journal.pbio.3001967.g001
DOI:
10.1371/journal.pbio.3001967.g002
DOI:
10.1371/journal.pbio.3001967.g003
DOI:
10.1371/journal.pbio.3001967.g004
DOI:
10.1371/journal.pbio.3001967.g005
DOI:
10.1371/journal.pbio.3001967.g006
DOI:
10.1371/journal.pbio.3001967.s001
DOI:
10.1371/journal.pbio.3001967.s002
DOI:
10.1371/journal.pbio.3001967.s003
DOI:
10.1371/journal.pbio.3001967.s004
DOI:
10.1371/journal.pbio.3001967.s005
DOI:
10.1371/journal.pbio.3001967.s006
DOI:
10.1371/journal.pbio.3001967.s007
DOI:
10.1371/journal.pbio.3001967.s008
DOI:
10.1371/journal.pbio.3001967.s009
DOI:
10.1371/journal.pbio.3001967.s010
DOI:
10.1371/journal.pbio.3001967.s011
DOI:
10.1371/journal.pbio.3001967.s012
DOI:
10.1371/journal.pbio.3001967.s013
DOI:
10.1371/journal.pbio.3001967.s014
DOI:
10.1371/journal.pbio.3001967.s015
DOI:
10.1371/journal.pbio.3001967.r001
DOI:
10.1371/journal.pbio.3001967.r002
DOI:
10.1371/journal.pbio.3001967.r003
DOI:
10.1371/journal.pbio.3001967.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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