Produção Nacional
Revisado por pares
A Biosafety Level 2 Mouse Model for Studying Betacoronavirus-Induced Acute Lung Damage and Systemic Manifestations
2021; American Society for Microbiology; Volume: 95; Issue: 22 Linguagem: Inglês
10.1128/jvi.01276-21
ISSN1098-5514
AutoresAna Cláudia dos Santos Pereira Andrade, Gabriel Henrique Campolina-Silva, Celso Martins Queiroz‐Junior, Leonardo Camilo de Oliveira, Larisse de Souza Barbosa Lacerda, Jordane Clarisse Pimenta, Filipe Resende, Ian de Meira Chaves, Ingredy Passos, Danielle Cunha Teixeira, Paloma Graziele Bittencourt‐Silva, Priscila Aparecida Costa Valadão, Leonardo Rossi-Oliveira, Maísa Mota Antunes, André Felipe Almeida Figueiredo, Natália Teixeira Wnuk, Jairo R. Temerozo, André C. Ferreira, Allysson Cramer, Cleida A. Oliveira, Ricardo Durães‐Carvalho, Clarice Weis Arns, Pedro Pires Goulart Guimarães, Guilherme Mattos Jardim Costa, Gustavo Batista Menezes, Cristina Guatimosim, Glauber S. F. da Silva, Thiago Moreno L. Souza, Breno Rocha Barrioni, Marivalda M. Pereira, Lirlândia P. Sousa, Mauro Martins Teixeira, Vivian Vasconcelos Costa,
Tópico(s)Animal Virus Infections Studies
ResumoThe emergence of life-threatening zoonotic diseases caused by betacoronaviruses, including the ongoing coronavirus disease 19 (COVID-19) pandemic, has highlighted the need for developing preclinical models mirroring respiratory and systemic pathophysiological manifestations seen in infected humans. Here, we showed that C57BL/6J wild-type mice intranasally inoculated with the murine betacoronavirus murine hepatitis coronavirus 3 (MHV-3) develop a robust inflammatory response leading to acute lung injuries, including alveolar edema, hemorrhage, and fibrin thrombi. Although such histopathological changes seemed to resolve as the infection advanced, they efficiently impaired respiratory function, as the infected mice displayed restricted lung distention and increased respiratory frequency and ventilation. Following respiratory manifestation, the MHV-3 infection became systemic, and a high virus burden could be detected in multiple organs along with morphological changes. The systemic manifestation of MHV-3 infection was also marked by a sharp drop in the number of circulating platelets and lymphocytes, besides the augmented concentration of the proinflammatory cytokines interleukin 1 beta (IL-1β), IL-6, IL-12, gamma interferon (IFN-γ), and tumor necrosis factor (TNF), thereby mirroring some clinical features observed in moderate and severe cases of COVID-19. Importantly, both respiratory and systemic changes triggered by MHV-3 infection were greatly prevented by blocking TNF signaling, either via genetic or pharmacologic approaches. In line with this, TNF blockage also diminished the infection-mediated release of proinflammatory cytokines and virus replication of human epithelial lung cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Collectively, results show that MHV-3 respiratory infection leads to a large range of clinical manifestations in mice and may constitute an attractive, lower-cost, biosafety level 2 (BSL2)
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