Author | Torices, Silvia | |
Author | Motta, Carolline | |
Author | Rosa, Barbara da | |
Author | Marcos, Anne | |
Author | Alvarez-Rosa, Liandra | |
Author | Siqueira, Michele | |
Author | Moreno-Rodriguez, Thaidy | |
Author | Matos, Aline | |
Author | Caetano, Braulia | |
Author | Martins, Jessica | |
Author | Gladulich, Luis | |
Author | Loiola, Erick | |
Author | Bagshaw, Olivia | |
Author | Stuart, Jeffrey | |
Author | Siqueira, Marilda | |
Author | Stipursky, Joice | |
Author | Toborek, Michal | |
Author | Adesse, Daniel | |
Access date | 2023-02-06T20:21:41Z | |
Available date | 2023-02-06T20:21:41Z | |
Document date | 2022 | |
Citation | TORICES, Silvia et al. SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling. | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/56903 | |
Description | DOI - 10.21203/rs.3.rs-1762855/v1 | en_US |
Language | eng | en_US |
Publisher | Research Square | en_US |
Rights | open access | en_US |
Subject in Portuguese | Infecção por SARS-CoV-2 | en_US |
Subject in Portuguese | Cérebro humano microvascular | en_US |
Subject in Portuguese | Células endoteliais leva à ativação inflamatória | en_US |
Subject in Portuguese | Via não canônica do NF-κB | en_US |
Subject in Portuguese | Remodelação mitocondrial | en_US |
Title | SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling | en_US |
Type | Article | en_US |
Abstract | Neurological effects of COVID-19 and long-COVID-19 as well as neuroinvasion by SARS-CoV-2 still pose
several questions and are of both clinical and scientific relevance. We described the cellular and
molecular effects of the human brain microvascular endothelial cells (HBMECs) in vitro infection by
SARS-CoV-2 to understand the underlying mechanisms of viral transmigration through the Blood-Brain
Barrier. Despite the low to non- productive viral replication, SARS-CoV-2-infected cultures displayed
increased apoptotic cell death and tight junction protein expression and immunolocalization.
Transcriptomic profiling of infected cultures revealed endothelial activation via NF-κB non-canonical
pathway, including RELB overexpression, and mitochondrial dysfunction. Additionally, SARS-CoV-2 led to
altered secretion of key angiogenic factors and to significant changes in mitochondrial dynamics, with
increased mitofusin-2 expression and increased mitochondrial networks. Endothelial activation and
remodeling can further contribute to neuroinflammatory processes and lead to further BBB permeability
in COVID-19. | en_US |
Affilliation | University of Miami Miller School of Medicine. | en_US |
Affilliation | Fundação Oswaldo Cruz | en_US |
Affilliation | Fundação Oswaldo Cruz | en_US |
Affilliation | Fundação Oswaldo Cruz | en_US |
Affilliation | Fundação Oswaldo Cruz | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. | en_US |
Affilliation | University of California San Francisco. San Fransisco, CA, USA. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratório e do Sarampo. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Fundacao Oswaldo Cruz | en_US |
Affilliation | Fundacao Oswaldo Cruz | en_US |
Affilliation | Fundacao Oswaldo Cruz | en_US |
Affilliation | Universidade Federal Fluminense. Niterói, RJ, Brasil. | en_US |
Affilliation | Brock University. | en_US |
Affilliation | Brock University. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brasil. | en_US |
Affilliation | University of Miami. USA. | en_US |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | en_US |
Subject | SARS-CoV-2 | en_US |
Subject | Infection of human brain | en_US |
Subject | Endothelial cells leads to inflammatory activation | en_US |
Subject | Through NF-κB non-canonical pathway | en_US |
Subject | Mitochondrial remodeling | en_US |