tetano
Editor, Senior Moderator
PLoS Biol
. 2022 Oct 13;20(10):e3001805.
doi: 10.1371/journal.pbio.3001805. Online ahead of print.
LRRC15 inhibits SARS-CoV-2 cellular entry in trans
Jaewon Song[SUP] 1 [/SUP], Ryan D Chow[SUP] 2 [/SUP], Mario Pena-Hernandez[SUP] 3 4 [/SUP], Li Zhang[SUP] 1 [/SUP], Skylar A Loeb[SUP] 1 [/SUP], Eui-Young So[SUP] 5 [/SUP], Olin D Liang[SUP] 5 [/SUP], Ping Ren[SUP] 2 [/SUP], Sidi Chen[SUP] 2 [/SUP], Craig B Wilen[SUP] 3 4 [/SUP], Sanghyun Lee[SUP] 1 [/SUP]
Affiliations
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is mediated by the entry receptor angiotensin-converting enzyme 2 (ACE2). Although attachment factors and coreceptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory attachment factor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single-cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not coexpressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory attachment factor for SARS-CoV-2 that regulates viral entry in trans.
. 2022 Oct 13;20(10):e3001805.
doi: 10.1371/journal.pbio.3001805. Online ahead of print.
LRRC15 inhibits SARS-CoV-2 cellular entry in trans
Jaewon Song[SUP] 1 [/SUP], Ryan D Chow[SUP] 2 [/SUP], Mario Pena-Hernandez[SUP] 3 4 [/SUP], Li Zhang[SUP] 1 [/SUP], Skylar A Loeb[SUP] 1 [/SUP], Eui-Young So[SUP] 5 [/SUP], Olin D Liang[SUP] 5 [/SUP], Ping Ren[SUP] 2 [/SUP], Sidi Chen[SUP] 2 [/SUP], Craig B Wilen[SUP] 3 4 [/SUP], Sanghyun Lee[SUP] 1 [/SUP]
Affiliations
- PMID: 36228039
- DOI: 10.1371/journal.pbio.3001805
Abstract
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is mediated by the entry receptor angiotensin-converting enzyme 2 (ACE2). Although attachment factors and coreceptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory attachment factor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single-cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not coexpressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory attachment factor for SARS-CoV-2 that regulates viral entry in trans.