Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus
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 and
Terence S. Dermody ()
Additional contact information
Pengcheng Shang: University of Pittsburgh School of Medicine
Joshua D. Simpson: Université catholique de Louvain
Gwen M. Taylor: University of Pittsburgh School of Medicine
Danica M. Sutherland: University of Pittsburgh School of Medicine
Olivia L. Welsh: University of Pittsburgh School of Medicine
Pavithra Aravamudhan: University of Pittsburgh School of Medicine
Rita Dos Santos Natividade: Université catholique de Louvain
Kristina Schwab: University of Pittsburgh School of Medicine
Joshua J. Michel: University of Pittsburgh School of Medicine
Amanda C. Poholek: University of Pittsburgh School of Medicine
Yijen Wu: University of Pittsburgh School of Medicine
Dhivyaa Rajasundaram: University of Pittsburgh School of Medicine
Melanie Koehler: Leibniz Institute for Food Systems Biology at the Technical University Munich
David Alsteens: Université catholique de Louvain
Terence S. Dermody: University of Pittsburgh School of Medicine
Nature Communications, 2023, vol. 14, issue 1, 1-15
Abstract:
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.
Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38327-6
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DOI: 10.1038/s41467-023-38327-6
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