Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mi...

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Autores: Vidal, Enric, López Figueroa, Carlos, Rodon, Jordi, Pérez, Mónica, Brustolin, Marco, Guallar, Víctor|||0000-0002-4580-1114
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/367820
Acceso en línea:https://hdl.handle.net/2117/367820
https://dx.doi.org/10.1177/03009858211066841
Access Level:acceso abierto
Palabra clave:COVID-19 (Disease)
Animal models in research
Neuropathology
SARS-CoV-2
Coronavirus Disease 2019
hACE2-transgenic mice,
Brain
Meningoencephalitis
Animal model
COVID-19 (Malaltia)
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
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repository_id_str
spelling Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic miceVidal, EnricLópez Figueroa, CarlosRodon, JordiPérez, MónicaBrustolin, MarcoGuallar, Víctor|||0000-0002-4580-1114COVID-19 (Disease)Animal models in researchNeuropathologySARS-CoV-2Coronavirus Disease 2019NeuropathologyhACE2-transgenic mice,BrainMeningoencephalitisAnimal modelCOVID-19 (Malaltia)Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::BioinformàticaSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The CBIG Consortium (constituted by IRTA-CReSA, BSC, and IrsiCaixa) is supported by Grifols pharmaceutical. The authors also acknowledge the crowdfunding initiative of https://www.yomecorono.com.Peer Reviewed"Article signat per 12 autors/es: Enric Vidal*, Carlos López-Figueroa*, Jordi Rodon, Mónica Pérez, Marco Brustolin, Guillermo Cantero, Víctor Guallar, Nuria Izquierdo-Useros, Jorge Carrillo, Julià Blanco, Bonaventura Clotet, Júlia Vergara-Alert, Joaquim Segalés"SAGE Publications20212021-12-0120222022-05-30journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/2117/367820https://dx.doi.org/10.1177/0300985821106684134955064reponame:UPCommons. Portal del coneixement obert de la UPCinstname:Universitat Politècnica de Catalunya (UPC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:upcommons.upc.edu:2117/3678202026-05-27T15:37:01Z
dc.title.none.fl_str_mv Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice
title Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice
spellingShingle Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice
Vidal, Enric
COVID-19 (Disease)
Animal models in research
Neuropathology
SARS-CoV-2
Coronavirus Disease 2019
Neuropathology
hACE2-transgenic mice,
Brain
Meningoencephalitis
Animal model
COVID-19 (Malaltia)
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
title_short Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice
title_full Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice
title_fullStr Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice
title_full_unstemmed Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice
title_sort Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice
dc.creator.none.fl_str_mv Vidal, Enric
López Figueroa, Carlos
Rodon, Jordi
Pérez, Mónica
Brustolin, Marco
Guallar, Víctor|||0000-0002-4580-1114
author Vidal, Enric
author_facet Vidal, Enric
López Figueroa, Carlos
Rodon, Jordi
Pérez, Mónica
Brustolin, Marco
Guallar, Víctor|||0000-0002-4580-1114
author_role author
author2 López Figueroa, Carlos
Rodon, Jordi
Pérez, Mónica
Brustolin, Marco
Guallar, Víctor|||0000-0002-4580-1114
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv COVID-19 (Disease)
Animal models in research
Neuropathology
SARS-CoV-2
Coronavirus Disease 2019
Neuropathology
hACE2-transgenic mice,
Brain
Meningoencephalitis
Animal model
COVID-19 (Malaltia)
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
topic COVID-19 (Disease)
Animal models in research
Neuropathology
SARS-CoV-2
Coronavirus Disease 2019
Neuropathology
hACE2-transgenic mice,
Brain
Meningoencephalitis
Animal model
COVID-19 (Malaltia)
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-12-01
2022
2022-05-30
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/2117/367820
https://dx.doi.org/10.1177/03009858211066841
34955064
url https://hdl.handle.net/2117/367820
https://dx.doi.org/10.1177/03009858211066841
identifier_str_mv 34955064
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv SAGE Publications
publisher.none.fl_str_mv SAGE Publications
dc.source.none.fl_str_mv reponame:UPCommons. Portal del coneixement obert de la UPC
instname:Universitat Politècnica de Catalunya (UPC)
instname_str Universitat Politècnica de Catalunya (UPC)
reponame_str UPCommons. Portal del coneixement obert de la UPC
collection UPCommons. Portal del coneixement obert de la UPC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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