Fibroblast-expressed LRRC15 suppresses SARS-CoV-2 infection and controls antiviral and antifibrotic transcriptional programs
Cold Spring Harbor Laboratory, 2021
Online
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Zugriff:
Although ACE2 is the primary receptor for 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 aTLR-related cell surface receptor calledleucine-rich repeat-containing protein 15(LRRC15).LRRC15expression was sufficient to promote SARS-CoV-2 Spike binding where they form a cell surface complex.LRRC15mRNA is expressed in human collagen-producing lung myofibroblasts and LRRC15 protein is induced in severe 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 intrans. 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.
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Fibroblast-expressed LRRC15 suppresses SARS-CoV-2 infection and controls antiviral and antifibrotic transcriptional programs
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Autor/in / Beteiligte Person: | Loo, Lipin ; Waller, Matthew A. ; Moreno, Cesar L. ; Cole, Alexander J. ; Alberto Ospina Stella ; Pop, Oltin-Tiberiu ; Jochum, Ann-Kristin ; Omar Hasan Ali ; Denes, Christopher E. ; Hamoudi, Zina ; Chung, Felicity ; Aggarwal, Anupriya ; Low, Jason K. K. ; Patel, Karishma ; Siddiquee, Rezwan ; Kang, Taeyoung ; Mathivanan, Suresh ; Mackay, Joel P. ; Flatz, Lukas ; Hesselson, Daniel ; Turville, Stuart ; G. Gregory Neely |
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Veröffentlichung: | Cold Spring Harbor Laboratory, 2021 |
Medientyp: | unknown |
DOI: | 10.1101/2021.11.09.467981 |
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