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; Terence S. Dermody

doi:10.1038/s41467-023-38327-6

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

Pengcheng Shang (First Author), Joshua D. Simpson (Co-Author), Gwen M. Taylor (Co-Author), Danica M. Sutherland (Co-Author), Olivia L. Welsh (Co-Author), Pavithra Aravamudhan (Co-Author), Rita Dos Santos Natividade (Co-Author), Kristina Schwab (Co-Author), Joshua J. Michel (Co-Author), Amanda C. Poholek (Co-Author), Yijen Wu (Co-Author), Dhivyaa Rajasundaram (Co-Author), Melanie Koehler (Co-Author), David Alsteens (Co-Author), Terence S. Dermody^* (Last Author)

^*Corresponding author for this work

Mechanoreceptors

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14 Scopus citations

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.

Original language	English
Article number	2615
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-38327-6
State	Published - Dec 2023

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Shang, P., Simpson, J. D., Taylor, G. M., Sutherland, D. M., Welsh, O. L., Aravamudhan, P., Natividade, R. D. S., Schwab, K., Michel, J. J., Poholek, A. C., Wu, Y., Rajasundaram, D., Koehler, M., Alsteens, D., & Dermody, T. S. (2023). Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus. Nature Communications, 14(1), Article 2615. https://doi.org/10.1038/s41467-023-38327-6

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title = "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-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.",

author = "Pengcheng Shang and Simpson, \{Joshua D.\} and Taylor, \{Gwen M.\} and Sutherland, \{Danica M.\} and Welsh, \{Olivia L.\} and Pavithra Aravamudhan and Natividade, \{Rita Dos Santos\} and Kristina Schwab and Michel, \{Joshua J.\} and Poholek, \{Amanda C.\} and Yijen Wu and Dhivyaa Rajasundaram and Melanie Koehler and David Alsteens and Dermody, \{Terence S.\}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-38327-6",

language = "English",

volume = "14",

journal = "Nature Communications",

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Shang, P, Simpson, JD, Taylor, GM, Sutherland, DM, Welsh, OL, Aravamudhan, P, Natividade, RDS, Schwab, K, Michel, JJ, Poholek, AC, Wu, Y, Rajasundaram, D, Koehler, M, Alsteens, D & Dermody, TS 2023, 'Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus', Nature Communications, vol. 14, no. 1, 2615. https://doi.org/10.1038/s41467-023-38327-6

TY - JOUR

T1 - Paired immunoglobulin-like receptor B is an entry receptor for mammalian orthoreovirus

AU - Shang, Pengcheng

AU - Simpson, Joshua D.

AU - Taylor, Gwen M.

AU - Sutherland, Danica M.

AU - Welsh, Olivia L.

AU - Aravamudhan, Pavithra

AU - Natividade, Rita Dos Santos

AU - Schwab, Kristina

AU - Michel, Joshua J.

AU - Poholek, Amanda C.

AU - Wu, Yijen

AU - Rajasundaram, Dhivyaa

AU - Koehler, Melanie

AU - Alsteens, David

AU - Dermody, Terence S.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85158958197

U2 - 10.1038/s41467-023-38327-6

DO - 10.1038/s41467-023-38327-6

M3 - Article

C2 - 37147336

AN - SCOPUS:85158958197

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 2615

ER -

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

Abstract

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