| Autor: |
Vivian Vasconcelos Costa, Lirlandia P. Sousa, Ana Cláudia dos Santos Pereira Andrade, Larisse de Souza Barbosa Lacerda, Gustavo B. Menezes, Marivalda M. Pereira, Jairo R. Temerozo, Ricardo Durães-Carvalho, Maísa Mota Antunes, Clarice Weis Arns, Leonardo Rossi-Oliveira, Gabriel Henrique Campolina-Silva, Priscila Aparecida Costa Valadão, Allysson Cramer, Filipe Resende Oliveira de Souza, Celso Martins Queiroz-Junior, Jordane Clarisse Pimenta, Mauro M. Teixeira, Pedro P.G. Guimarães, Ingredy Passos, Thiago Moreno L. Souza, A. F. A. Figueiredo, Paloma Graziele Bittencourt-Silva, Leonardo C. De Oliveira, Breno Rocha Barrioni, Ian de Meira Chaves, Natalia Teixeira Wnuk, Glauber S. F. da Silva, Cleida A. Oliveira, Cristina Guatimosim, Guilherme M.J. Costa, Danielle Cunha Teixeira, André C. Ferreira |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.05.28.446200 |
| Popis: |
Several animal models are being used to explore important features of COVID-19, nevertheless none of them recapitulates all aspects of the disease in humans. The continuous refinement and development of other options ofin vivomodels are opportune, especially ones that are carried out at BSL-2 (Biosafety Level 2) laboratories. In this study, we investigated the suitability of the intranasal infection with the murine betacoronavirus MHV-3 to recapitulate multiple aspects of the pathogenesis of COVID-19 in C57BL/6J mice. We demonstrate that MHV-3 replicated in lungs 1 day after inoculation and triggered respiratory inflammation and dysfunction. This MHV-model of infection was further applied to highlight the critical role of TNF in cytokine-mediated coronavirus pathogenesis. Blocking TNF signaling by pharmacological and genetic strategies greatly increased the survival time and reduces lung injury of MHV-3-infected mice.In vitrostudies showed that TNF blockage decreased SARS-CoV-2 replication in human epithelial lung cells and resulted in the lower release of IL-6 and IL-8 cytokines beyond TNF itself. Taken together, our results demonstrate that this model of MHV infection in mice is a useful BSL-2 screening platform for evaluating pathogenesis for human coronaviruses infections, such as COVID-19. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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