Glycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus

ABSTRACT Receptors expressed on the host cell surface adhere viruses to target cells and serve as determinants of viral tropism. Several viruses bind cell surface glycans to facilitate entry, but the contribution of specific glycan moieties to viral disease is incompletely understood. Reovirus provi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jennifer Stencel-Baerenwald, Kerstin Reiss, Bärbel S. Blaum, Daniel Colvin, Xiao-Nan Li, Ty Abel, Kelli Boyd, Thilo Stehle, Terence S. Dermody
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f71c375a9bb248dd95d71175cfb81077
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f71c375a9bb248dd95d71175cfb81077
record_format	dspace
spelling	oai:doaj.org-article:f71c375a9bb248dd95d71175cfb810772021-11-15T15:41:33ZGlycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus10.1128/mBio.02356-142150-7511https://doaj.org/article/f71c375a9bb248dd95d71175cfb810772015-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02356-14https://doaj.org/toc/2150-7511ABSTRACT Receptors expressed on the host cell surface adhere viruses to target cells and serve as determinants of viral tropism. Several viruses bind cell surface glycans to facilitate entry, but the contribution of specific glycan moieties to viral disease is incompletely understood. Reovirus provides a tractable experimental model for studies of viral neuropathogenesis. In newborn mice, serotype 1 (T1) reovirus causes hydrocephalus, whereas serotype 3 (T3) reovirus causes encephalitis. T1 and T3 reoviruses engage distinct glycans, suggesting that glycan-binding capacity contributes to these differences in pathogenesis. Using structure-guided mutagenesis, we engineered a mutant T1 reovirus incapable of binding the T1 reovirus-specific glycan receptor, GM2. The mutant virus induced substantially less hydrocephalus than wild-type virus, an effect phenocopied by wild-type virus infection of GM2-deficient mice. In comparison to wild-type virus, yields of mutant virus were diminished in cultured ependymal cells, the cell type that lines the brain ventricles. These findings suggest that GM2 engagement targets reovirus to ependymal cells in mice and illuminate the function of glycan engagement in reovirus serotype-dependent disease. IMPORTANCE Receptor utilization strongly influences viral disease, often dictating host range and target cell selection. Different reovirus serotypes bind to different glycans, but a precise function for these molecules in pathogenesis is unknown. We used type 1 (T1) reovirus deficient in binding the GM2 glycan and mice lacking GM2 to pinpoint a role for glycan engagement in hydrocephalus caused by T1 reovirus. This work indicates that engagement of a specific glycan can lead to infection of specific cells in the host and consequent disease at that site. Since reovirus is being developed as a vaccine vector and oncolytic agent, understanding reovirus-glycan interactions may allow manipulation of reovirus glycan-binding properties for therapeutic applications.Jennifer Stencel-BaerenwaldKerstin ReissBärbel S. BlaumDaniel ColvinXiao-Nan LiTy AbelKelli BoydThilo StehleTerence S. DermodyAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 2 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jennifer Stencel-Baerenwald Kerstin Reiss Bärbel S. Blaum Daniel Colvin Xiao-Nan Li Ty Abel Kelli Boyd Thilo Stehle Terence S. Dermody Glycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus
description	ABSTRACT Receptors expressed on the host cell surface adhere viruses to target cells and serve as determinants of viral tropism. Several viruses bind cell surface glycans to facilitate entry, but the contribution of specific glycan moieties to viral disease is incompletely understood. Reovirus provides a tractable experimental model for studies of viral neuropathogenesis. In newborn mice, serotype 1 (T1) reovirus causes hydrocephalus, whereas serotype 3 (T3) reovirus causes encephalitis. T1 and T3 reoviruses engage distinct glycans, suggesting that glycan-binding capacity contributes to these differences in pathogenesis. Using structure-guided mutagenesis, we engineered a mutant T1 reovirus incapable of binding the T1 reovirus-specific glycan receptor, GM2. The mutant virus induced substantially less hydrocephalus than wild-type virus, an effect phenocopied by wild-type virus infection of GM2-deficient mice. In comparison to wild-type virus, yields of mutant virus were diminished in cultured ependymal cells, the cell type that lines the brain ventricles. These findings suggest that GM2 engagement targets reovirus to ependymal cells in mice and illuminate the function of glycan engagement in reovirus serotype-dependent disease. IMPORTANCE Receptor utilization strongly influences viral disease, often dictating host range and target cell selection. Different reovirus serotypes bind to different glycans, but a precise function for these molecules in pathogenesis is unknown. We used type 1 (T1) reovirus deficient in binding the GM2 glycan and mice lacking GM2 to pinpoint a role for glycan engagement in hydrocephalus caused by T1 reovirus. This work indicates that engagement of a specific glycan can lead to infection of specific cells in the host and consequent disease at that site. Since reovirus is being developed as a vaccine vector and oncolytic agent, understanding reovirus-glycan interactions may allow manipulation of reovirus glycan-binding properties for therapeutic applications.
format	article
author	Jennifer Stencel-Baerenwald Kerstin Reiss Bärbel S. Blaum Daniel Colvin Xiao-Nan Li Ty Abel Kelli Boyd Thilo Stehle Terence S. Dermody
author_facet	Jennifer Stencel-Baerenwald Kerstin Reiss Bärbel S. Blaum Daniel Colvin Xiao-Nan Li Ty Abel Kelli Boyd Thilo Stehle Terence S. Dermody
author_sort	Jennifer Stencel-Baerenwald
title	Glycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus
title_short	Glycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus
title_full	Glycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus
title_fullStr	Glycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus
title_full_unstemmed	Glycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus
title_sort	glycan engagement dictates hydrocephalus induction by serotype 1 reovirus
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/f71c375a9bb248dd95d71175cfb81077
work_keys_str_mv	AT jenniferstencelbaerenwald glycanengagementdictateshydrocephalusinductionbyserotype1reovirus AT kerstinreiss glycanengagementdictateshydrocephalusinductionbyserotype1reovirus AT barbelsblaum glycanengagementdictateshydrocephalusinductionbyserotype1reovirus AT danielcolvin glycanengagementdictateshydrocephalusinductionbyserotype1reovirus AT xiaonanli glycanengagementdictateshydrocephalusinductionbyserotype1reovirus AT tyabel glycanengagementdictateshydrocephalusinductionbyserotype1reovirus AT kelliboyd glycanengagementdictateshydrocephalusinductionbyserotype1reovirus AT thilostehle glycanengagementdictateshydrocephalusinductionbyserotype1reovirus AT terencesdermody glycanengagementdictateshydrocephalusinductionbyserotype1reovirus
_version_	1718427681652998144

Glycan Engagement Dictates Hydrocephalus Induction by Serotype 1 Reovirus

Ejemplares similares