Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus
Abstract Mammalian orthoreovirus (reovirus) infects most mammals and is associated with celiac disease in humans. In mice, reovirus infects the intestine and disseminates systemically to cause serotype-specific patterns of disease in the brain. To identify receptors conferring reovirus serotype-depe...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38327-6 |
| _version_ | 1797832013559889920 |
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| author | Pengcheng Shang Joshua D. Simpson Gwen M. Taylor Danica M. Sutherland Olivia L. Welsh Pavithra Aravamudhan Rita Dos Santos Natividade Kristina Schwab Joshua J. Michel Amanda C. Poholek Yijen Wu Dhivyaa Rajasundaram Melanie Koehler David Alsteens Terence S. Dermody |
| author_facet | Pengcheng Shang Joshua D. Simpson Gwen M. Taylor Danica M. Sutherland Olivia L. Welsh Pavithra Aravamudhan Rita Dos Santos Natividade Kristina Schwab Joshua J. Michel Amanda C. Poholek Yijen Wu Dhivyaa Rajasundaram Melanie Koehler David Alsteens Terence S. Dermody |
| author_sort | Pengcheng Shang |
| collection | DOAJ |
| description | Abstract Mammalian orthoreovirus (reovirus) infects most mammals and is associated with celiac disease in humans. In mice, reovirus infects the intestine and disseminates systemically to cause serotype-specific patterns of disease in the brain. To identify receptors conferring reovirus serotype-dependent neuropathogenesis, we conducted a genome-wide CRISPRa screen and identified paired immunoglobulin-like receptor B (PirB) as a receptor candidate. Ectopic expression of PirB allowed reovirus binding and infection. PirB extracelluar D3D4 region is required for reovirus attachment and infectivity. Reovirus binds to PirB with nM affinity as determined by single molecule force spectroscopy. Efficient reovirus endocytosis requires PirB signaling motifs. In inoculated mice, PirB is required for maximal replication in the brain and full neuropathogenicity of neurotropic serotype 3 (T3) reovirus. In primary cortical neurons, PirB expression contributes to T3 reovirus infectivity. Thus, PirB is an entry receptor for reovirus and contributes to T3 reovirus replication and pathogenesis in the murine brain. |
| first_indexed | 2024-04-09T14:00:56Z |
| format | Article |
| id | doaj.art-3daf5306cc154b38afd87eb89709065d |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T14:00:56Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-3daf5306cc154b38afd87eb89709065d2023-05-07T11:17:54ZengNature PortfolioNature Communications2041-17232023-05-0114111510.1038/s41467-023-38327-6Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirusPengcheng Shang0Joshua D. Simpson1Gwen M. Taylor2Danica M. Sutherland3Olivia L. Welsh4Pavithra Aravamudhan5Rita Dos Santos Natividade6Kristina Schwab7Joshua J. Michel8Amanda C. Poholek9Yijen Wu10Dhivyaa Rajasundaram11Melanie Koehler12David Alsteens13Terence S. Dermody14Department of Pediatrics, University of Pittsburgh School of MedicineLouvain Institute of Biomolecular Science and Technology, Université catholique de LouvainDepartment of Pediatrics, University of Pittsburgh School of MedicineDepartment of Pediatrics, University of Pittsburgh School of MedicineDepartment of Pediatrics, University of Pittsburgh School of MedicineDepartment of Pediatrics, University of Pittsburgh School of MedicineLouvain Institute of Biomolecular Science and Technology, Université catholique de LouvainDepartment of Immunology, University of Pittsburgh School of MedicineDepartment of Pediatrics, University of Pittsburgh School of MedicineDepartment of Pediatrics, University of Pittsburgh School of MedicineDepartment of Developmental Biology, University of Pittsburgh School of MedicineDepartment of Pediatrics, University of Pittsburgh School of MedicineLeibniz Institute for Food Systems Biology at the Technical University MunichLouvain Institute of Biomolecular Science and Technology, Université catholique de LouvainDepartment of Pediatrics, University of Pittsburgh School of MedicineAbstract Mammalian orthoreovirus (reovirus) infects most mammals and is associated with celiac disease in humans. In mice, reovirus infects the intestine and disseminates systemically to cause serotype-specific patterns of disease in the brain. To identify receptors conferring reovirus serotype-dependent neuropathogenesis, we conducted a genome-wide CRISPRa screen and identified paired immunoglobulin-like receptor B (PirB) as a receptor candidate. Ectopic expression of PirB allowed reovirus binding and infection. PirB extracelluar D3D4 region is required for reovirus attachment and infectivity. Reovirus binds to PirB with nM affinity as determined by single molecule force spectroscopy. Efficient reovirus endocytosis requires PirB signaling motifs. In inoculated mice, PirB is required for maximal replication in the brain and full neuropathogenicity of neurotropic serotype 3 (T3) reovirus. In primary cortical neurons, PirB expression contributes to T3 reovirus infectivity. Thus, PirB is an entry receptor for reovirus and contributes to T3 reovirus replication and pathogenesis in the murine brain.https://doi.org/10.1038/s41467-023-38327-6 |
| spellingShingle | Pengcheng Shang Joshua D. Simpson Gwen M. Taylor Danica M. Sutherland Olivia L. Welsh Pavithra Aravamudhan Rita Dos Santos Natividade Kristina Schwab Joshua J. Michel Amanda C. Poholek Yijen Wu Dhivyaa Rajasundaram Melanie Koehler David Alsteens Terence S. Dermody Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus Nature Communications |
| title | Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus |
| title_full | Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus |
| title_fullStr | Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus |
| title_full_unstemmed | Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus |
| title_short | Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus |
| title_sort | paired immunoglobulin like receptor b is an entry receptor for mammalian orthoreovirus |
| url | https://doi.org/10.1038/s41467-023-38327-6 |
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