Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus

Author:

Shang PengchengORCID,Simpson Joshua D.ORCID,Taylor Gwen M.ORCID,Sutherland Danica M.ORCID,Welsh Olivia L.,Aravamudhan Pavithra,Natividade Rita Dos SantosORCID,Schwab Kristina,Michel Joshua J.,Poholek Amanda C.ORCID,Wu YijenORCID,Rajasundaram Dhivyaa,Koehler Melanie,Alsteens DavidORCID,Dermody Terence S.ORCID

Abstract

AbstractMammalian 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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