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LRRC15 mediates an accessory interaction with the SARS-CoV-2 spike protein.
Shilts, Jarrod; Crozier, Thomas W M; Teixeira-Silva, Ana; Gabaev, Ildar; Gerber, Pehuén Pereyra; Greenwood, Edward J D; Watson, Samuel James; Ortmann, Brian M; Gawden-Bone, Christian M; Pauzaite, Tekle; Hoffmann, Markus; Nathan, James A; Pöhlmann, Stefan; Matheson, Nicholas J; Lehner, Paul J; Wright, Gavin J.
  • Shilts J; Cell Surface Signalling Laboratory, Wellcome Sanger Institute, Cambridge, United Kingdom.
  • Crozier TWM; Department of Biology, Hull York Medical School, York Biomedical Research Institute, University of York, York, United Kingdom.
  • Teixeira-Silva A; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Gabaev I; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Gerber PP; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Greenwood EJD; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Watson SJ; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Ortmann BM; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Gawden-Bone CM; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Pauzaite T; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Hoffmann M; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Nathan JA; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.
  • Pöhlmann S; Faculty of Biology and Psychology, Georg-August University Göttingen, Göttingen, Germany.
  • Matheson NJ; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, United Kingdom.
  • Lehner PJ; Infection Biology Unit, German Primate Center - Leibniz Institute for Primate Research, Göttingen, Germany.
  • Wright GJ; Faculty of Biology and Psychology, Georg-August University Göttingen, Göttingen, Germany.
PLoS Biol ; 21(2): e3001959, 2023 02.
Article in English | MEDLINE | ID: covidwho-2235567
ABSTRACT
The interactions between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead to Coronavirus Disease 2019 (COVID-19). The spike protein is the largest structural component of the virus and mediates interactions essential for infection, including with the primary angiotensin-converting enzyme 2 (ACE2) receptor. We performed two independent cell-based systematic screens to determine whether there are additional proteins by which the spike protein of SARS-CoV-2 can interact with human cells. We discovered that in addition to ACE2, expression of LRRC15 also causes spike protein binding. This interaction is distinct from other known spike attachment mechanisms such as heparan sulfates or lectin receptors. Measurements of orthologous coronavirus spike proteins implied the interaction was functionally restricted to SARS-CoV-2 by accessibility. We localized the interaction to the C-terminus of the S1 domain and showed that LRRC15 shares recognition of the ACE2 receptor binding domain. From analyzing proteomics and single-cell transcriptomics, we identify LRRC15 expression as being common in human lung vasculature cells and fibroblasts. Levels of LRRC15 were greatly elevated by inflammatory signals in the lungs of COVID-19 patients. Although infection assays demonstrated that LRRC15 alone is not sufficient to permit viral entry, we present evidence that it can modulate infection of human cells. This unexpected interaction merits further investigation to determine how SARS-CoV-2 exploits host LRRC15 and whether it could account for any of the distinctive features of COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Systematic review/Meta Analysis Limits: Humans Language: English Journal: PLoS Biol Journal subject: Biology Year: 2023 Document Type: Article Affiliation country: Journal.pbio.3001959

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Systematic review/Meta Analysis Limits: Humans Language: English Journal: PLoS Biol Journal subject: Biology Year: 2023 Document Type: Article Affiliation country: Journal.pbio.3001959