Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape

Kolawole, Abimbola O.; Mirabelli, Carmen; Hill, David R.; Svoboda, Sophia A.; Janowski, Andrew B.; Passalacqua, Karla D.; Rodriguez, Benancio N.; Dame, Michael K.; Freiden, Pamela; Berger, Ryan P.; Vu Cantero, Diem-Lan; Hosmillo, Myra; O'Riordan, Mary X.D.; Schultz-Cherry, Stacey; Guix Arnau, Susana; Spence, Jason R.; Wang, David; Wobus, Christiane E.

Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape

Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the...

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Detalles Bibliográficos
Autores:	Kolawole, Abimbola O., Mirabelli, Carmen, Hill, David R., Svoboda, Sophia A., Janowski, Andrew B., Passalacqua, Karla D., Rodriguez, Benancio N., Dame, Michael K., Freiden, Pamela, Berger, Ryan P., Vu Cantero, Diem-Lan, Hosmillo, Myra, O'Riordan, Mary X.D., Schultz-Cherry, Stacey, Guix Arnau, Susana, Spence, Jason R., Wang, David, Wobus, Christiane E.
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2019
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/158016
Acceso en línea:	https://hdl.handle.net/2445/158016
Access Level:	acceso abierto
Palabra clave:	Virologia Malalties intestinals Virology Intestinal diseases

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spelling	Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscapeKolawole, Abimbola O.Mirabelli, CarmenHill, David R.Svoboda, Sophia A.Janowski, Andrew B.Passalacqua, Karla D.Rodriguez, Benancio N.Dame, Michael K.Freiden, PamelaBerger, Ryan P.Vu Cantero, Diem-LanHosmillo, MyraO'Riordan, Mary X.D.Schultz-Cherry, StaceyGuix Arnau, SusanaSpence, Jason R.Wang, DavidWobus, Christiane E.VirologiaMalalties intestinalsVirologyIntestinal diseasesHuman astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE derived from different patients and from different intestinal regions independent of the cellular differentiation status. Flow cytometry and immunofluorescence analysis revealed that VA1 infects several cell types, including intestinal progenitor cells and mature enterocytes, in HIE cultures. RNA profiling of VA1-infected HIE uncovered that the host response to infection is dominated by interferon (IFN)-mediated innate immune responses. A comparison of the antiviral host response in non-transformed HIE and transformed human colon carcinoma Caco-2 cells highlighted significant differences between these cells, including an increased magnitude of the response in HIE. Additional studies confirmed the sensitivity of VA1 to exogenous IFNs, and indicated that the endogenous IFN response of HIE to curtail the growth of strains from all three clades. Genotypic variation in the permissiveness of different HIE lines to HAstV could be overcome by pharmacologic inhibition of JAK/STAT signaling. Collectively, our data identify HIE as a universal infection model for HAstV and an improved model of the intestinal epithelium to investigate enteric virus-host interactions.Public Library of Science (PLoS)2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion30 p.application/pdfhttps://hdl.handle.net/2445/158016Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.ppat.1008057PLoS Pathogens, 2019, vol. 15, num. 10, p. e1008057https://doi.org/10.1371/journal.ppat.1008057cc-by (c) Kolawole, Abimbola O. et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1580162026-05-29T05:05:01Z
dc.title.none.fl_str_mv	Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape
title	Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape
spellingShingle	Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape Kolawole, Abimbola O. Virologia Malalties intestinals Virology Intestinal diseases
title_short	Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape
title_full	Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape
title_fullStr	Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape
title_full_unstemmed	Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape
title_sort	Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape
dc.creator.none.fl_str_mv	Kolawole, Abimbola O. Mirabelli, Carmen Hill, David R. Svoboda, Sophia A. Janowski, Andrew B. Passalacqua, Karla D. Rodriguez, Benancio N. Dame, Michael K. Freiden, Pamela Berger, Ryan P. Vu Cantero, Diem-Lan Hosmillo, Myra O'Riordan, Mary X.D. Schultz-Cherry, Stacey Guix Arnau, Susana Spence, Jason R. Wang, David Wobus, Christiane E.
author	Kolawole, Abimbola O.
author_facet	Kolawole, Abimbola O. Mirabelli, Carmen Hill, David R. Svoboda, Sophia A. Janowski, Andrew B. Passalacqua, Karla D. Rodriguez, Benancio N. Dame, Michael K. Freiden, Pamela Berger, Ryan P. Vu Cantero, Diem-Lan Hosmillo, Myra O'Riordan, Mary X.D. Schultz-Cherry, Stacey Guix Arnau, Susana Spence, Jason R. Wang, David Wobus, Christiane E.
author_role	author
author2	Mirabelli, Carmen Hill, David R. Svoboda, Sophia A. Janowski, Andrew B. Passalacqua, Karla D. Rodriguez, Benancio N. Dame, Michael K. Freiden, Pamela Berger, Ryan P. Vu Cantero, Diem-Lan Hosmillo, Myra O'Riordan, Mary X.D. Schultz-Cherry, Stacey Guix Arnau, Susana Spence, Jason R. Wang, David Wobus, Christiane E.
author2_role	author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Virologia Malalties intestinals Virology Intestinal diseases
topic	Virologia Malalties intestinals Virology Intestinal diseases
description	Human astroviruses (HAstV) are understudied positive-strand RNA viruses that cause gastroenteritis mostly in children and the elderly. Three clades of astroviruses, classic, MLB-type and VA-type have been reported in humans. One limitation towards a better understanding of these viruses has been the lack of a physiologically relevant cell culture model that supports growth of all clades of HAstV. Herein, we demonstrate infection of HAstV strains belonging to all three clades in epithelium-only human intestinal enteroids (HIE) isolated from biopsy-derived intestinal crypts. A detailed investigation of infection of VA1, a member of the non-canonical HAstV-VA/HMO clade, showed robust replication in HIE derived from different patients and from different intestinal regions independent of the cellular differentiation status. Flow cytometry and immunofluorescence analysis revealed that VA1 infects several cell types, including intestinal progenitor cells and mature enterocytes, in HIE cultures. RNA profiling of VA1-infected HIE uncovered that the host response to infection is dominated by interferon (IFN)-mediated innate immune responses. A comparison of the antiviral host response in non-transformed HIE and transformed human colon carcinoma Caco-2 cells highlighted significant differences between these cells, including an increased magnitude of the response in HIE. Additional studies confirmed the sensitivity of VA1 to exogenous IFNs, and indicated that the endogenous IFN response of HIE to curtail the growth of strains from all three clades. Genotypic variation in the permissiveness of different HIE lines to HAstV could be overcome by pharmacologic inhibition of JAK/STAT signaling. Collectively, our data identify HIE as a universal infection model for HAstV and an improved model of the intestinal epithelium to investigate enteric virus-host interactions.
publishDate	2019
dc.date.none.fl_str_mv	2019 2020 2020 2020
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/158016
url	https://hdl.handle.net/2445/158016
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1371/journal.ppat.1008057 PLoS Pathogens, 2019, vol. 15, num. 10, p. e1008057 https://doi.org/10.1371/journal.ppat.1008057
dc.rights.none.fl_str_mv	cc-by (c) Kolawole, Abimbola O. et al., 2019 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) Kolawole, Abimbola O. et al., 2019 http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	30 p. application/pdf
dc.publisher.none.fl_str_mv	Public Library of Science (PLoS)
publisher.none.fl_str_mv	Public Library of Science (PLoS)
dc.source.none.fl_str_mv	Articles publicats en revistes (Genètica, Microbiologia i Estadística) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Astrovirus replication in human intestinal enteroids reveals multi-cellular tropism and an intricate host innate immune landscape

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