LRRC15 is an inhibitory receptor blocking SARS-CoV-2 spike-mediated entry in trans.
Jaewon SongRyan D ChowMario Pena-HernandezLi ZhangSkylar A LoebEui-Young SoOlin D LiangCraig B WilenSanghyun LeePublished in: bioRxiv : the preprint server for biology (2021)
SARS-CoV-2 infection is mediated by the entry receptor ACE2. Although attachment factors and co-receptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surface ome CRISPR activation screen, we identified human LRRC15 as an inhibitory receptor 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 co-expressed 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 receptor for SARS-CoV-2 regulating viral entry in trans .
Keyphrases
- sars cov
- single cell
- respiratory syndrome coronavirus
- binding protein
- angiotensin ii
- rna seq
- angiotensin converting enzyme
- poor prognosis
- endothelial cells
- signaling pathway
- induced apoptosis
- multidrug resistant
- gene expression
- high throughput
- dna methylation
- high intensity
- transcription factor
- genome wide
- cell proliferation