Author:
dos Santos Pereira Andrade Ana Cláudia,Campolina-Silva Gabriel Henrique,Queiroz-Junior Celso Martins,de Oliveira Leonardo Camilo,de Souza Barbosa Lacerda Larisse,Pimenta Jordane Clarisse,de Souza Filipe Resende Oliveira,de Meira Chaves Ian,Passos Ingredy Beatriz,Teixeira Danielle Cunha,Bittencourt-Silva Paloma Graziele,Costa Valadão Priscila Aparecida,Rossi-Oliveira Leonardo,Antunes Maisa Mota,Almeida Figueiredo André Felipe,Wnuk Natália Teixeira,Temerozo Jairo R.,Ferreira André Costa,Cramer Allysson,Oliveira Cleida Aparecida,Durães-Carvalho Ricardo,Arns Clarice Weis,Guimarães Pedro Pires Goulart,Costa Guilherme Mattos Jardim,de Menezes Gustavo Batista,Guatimosim Cristina,da Silva Glauber Santos Ferreira,Souza Thiago Moreno L.,Barrioni Breno Rocha,de Magalhães Pereira Marivalda,de Sousa Lirlândia Pires,Teixeira Mauro Martins,Costa Vivian Vasconcelos
Abstract
AbstractSeveral 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 of in vivo models 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 vitro studies 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.
Publisher
Cold Spring Harbor Laboratory