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 Barba, Enric|||0000-0002-4965-3286, López-Figueroa, Carlos|||0000-0002-1900-3469, Rodon, Jordi|||0000-0002-1032-9091, Pérez, Mónica, Brustolin, Marco|||0000-0002-3594-4488, Cantero, Guillermo|||0000-0003-4200-503X, Guallar, Victor|||0000-0002-4580-1114, Izquierdo Useros, Nuria|||0000-0002-1039-1821, Carrillo, Jorge|||0000-0003-0221-5948, Blanco, Julià|||0000-0002-2225-0217, Clotet Sala, Bonaventura|||0000-0003-3232-4598, Vergara-Alert, Júlia|||0000-0001-7484-444X, Segalés Coma, Joaquim|||0000-0002-1539-7261
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:266212
Acceso en línea:https://ddd.uab.cat/record/266212
https://dx.doi.org/urn:doi:10.1177/03009858211066841
Access Level:acceso abierto
Palabra clave:SARS-CoV-2
Coronavirus Disease 2019
Neuropathology
Hace2-transgenic mice
Brain
Meningoencephalitis
Animal model
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spelling Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic miceVidal Barba, Enric|||0000-0002-4965-3286López-Figueroa, Carlos|||0000-0002-1900-3469Rodon, Jordi|||0000-0002-1032-9091Pérez, MónicaBrustolin, Marco|||0000-0002-3594-4488Cantero, Guillermo|||0000-0003-4200-503XGuallar, Victor|||0000-0002-4580-1114Izquierdo Useros, Nuria|||0000-0002-1039-1821Carrillo, Jorge|||0000-0003-0221-5948Blanco, Julià|||0000-0002-2225-0217Clotet Sala, Bonaventura|||0000-0003-3232-4598Vergara-Alert, Júlia|||0000-0001-7484-444XSegalés Coma, Joaquim|||0000-0002-1539-7261SARS-CoV-2Coronavirus Disease 2019NeuropathologyHace2-transgenic miceBrainMeningoencephalitisAnimal modelSevere 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. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/266212https://dx.doi.org/urn:doi:10.1177/03009858211066841reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2662122026-06-06T12:50:31Z
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 Barba, Enric|||0000-0002-4965-3286
SARS-CoV-2
Coronavirus Disease 2019
Neuropathology
Hace2-transgenic mice
Brain
Meningoencephalitis
Animal model
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 Barba, Enric|||0000-0002-4965-3286
López-Figueroa, Carlos|||0000-0002-1900-3469
Rodon, Jordi|||0000-0002-1032-9091
Pérez, Mónica
Brustolin, Marco|||0000-0002-3594-4488
Cantero, Guillermo|||0000-0003-4200-503X
Guallar, Victor|||0000-0002-4580-1114
Izquierdo Useros, Nuria|||0000-0002-1039-1821
Carrillo, Jorge|||0000-0003-0221-5948
Blanco, Julià|||0000-0002-2225-0217
Clotet Sala, Bonaventura|||0000-0003-3232-4598
Vergara-Alert, Júlia|||0000-0001-7484-444X
Segalés Coma, Joaquim|||0000-0002-1539-7261
author Vidal Barba, Enric|||0000-0002-4965-3286
author_facet Vidal Barba, Enric|||0000-0002-4965-3286
López-Figueroa, Carlos|||0000-0002-1900-3469
Rodon, Jordi|||0000-0002-1032-9091
Pérez, Mónica
Brustolin, Marco|||0000-0002-3594-4488
Cantero, Guillermo|||0000-0003-4200-503X
Guallar, Victor|||0000-0002-4580-1114
Izquierdo Useros, Nuria|||0000-0002-1039-1821
Carrillo, Jorge|||0000-0003-0221-5948
Blanco, Julià|||0000-0002-2225-0217
Clotet Sala, Bonaventura|||0000-0003-3232-4598
Vergara-Alert, Júlia|||0000-0001-7484-444X
Segalés Coma, Joaquim|||0000-0002-1539-7261
author_role author
author2 López-Figueroa, Carlos|||0000-0002-1900-3469
Rodon, Jordi|||0000-0002-1032-9091
Pérez, Mónica
Brustolin, Marco|||0000-0002-3594-4488
Cantero, Guillermo|||0000-0003-4200-503X
Guallar, Victor|||0000-0002-4580-1114
Izquierdo Useros, Nuria|||0000-0002-1039-1821
Carrillo, Jorge|||0000-0003-0221-5948
Blanco, Julià|||0000-0002-2225-0217
Clotet Sala, Bonaventura|||0000-0003-3232-4598
Vergara-Alert, Júlia|||0000-0001-7484-444X
Segalés Coma, Joaquim|||0000-0002-1539-7261
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SARS-CoV-2
Coronavirus Disease 2019
Neuropathology
Hace2-transgenic mice
Brain
Meningoencephalitis
Animal model
topic SARS-CoV-2
Coronavirus Disease 2019
Neuropathology
Hace2-transgenic mice
Brain
Meningoencephalitis
Animal model
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 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv 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://ddd.uab.cat/record/266212
https://dx.doi.org/urn:doi:10.1177/03009858211066841
url https://ddd.uab.cat/record/266212
https://dx.doi.org/urn:doi:10.1177/03009858211066841
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
https://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
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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