Evidence map›Paper›PMID 34495692›Full record

ArticleJournal of virology2021

A Biosafety Level 2 Mouse Model for Studying Betacoronavirus-Induced Acute Lung Damage and Systemic Manifestations.

Ana Cláudia Dos Santos Pereira Andrade, Gabriel Henrique Campolina-Silva, Celso Martins Queiroz-Junior, Leonardo Camilo de Oliveira, Larisse de Souza Barbosa Lacerda, Jordane C Pimenta, Filipe Resende Oliveira de Souza, Ian de Meira Chaves, Ingredy Beatriz Passos, Danielle Cunha Teixeira and 23 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.5field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 52 citations in OpenAlex.

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  3. In Vivo Preclinical Platforms to Study Coronavirus Infection.Methods in molecular biology (Clifton, N.J.) · 2026
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  4. Cytosolic proliferating cell nuclear antigen (PCNA) orchestrates neutrophil hyperactivation in COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  10. Angiotensin-(1-7) decreases inflammation and lung damage caused by betacoronavirus infection in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors at 4 institutions in 1 country.

Ana Cláudia Dos Santos Pereira Andrade *Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Gabriel Henrique Campolina-Silva *Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Celso Martins Queiroz-JuniorDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Leonardo Camilo de OliveiraDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Larisse de Souza Barbosa LacerdaDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Jordane C PimentaDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Filipe Resende Oliveira de SouzaDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Ian de Meira ChavesDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Ingredy Beatriz PassosDepartment of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Danielle Cunha TeixeiraDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Paloma Graziele Bittencourt-SilvaDepartment of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Priscila Aparecida Costa ValadãoDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Leonardo Rossi-OliveiraDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Maisa Mota AntunesDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
André Felipe Almeida FigueiredoDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Natália Teixeira WnukDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Jairo R TemerozoLaboratory on Thymus Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, RJ, Brazil.ORCID 0000-0002-8092-2149
André Costa FerreiraNational Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDNP), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
Allysson CramerDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Cleida Aparecida OliveiraDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Ricardo Durães-CarvalhoLaboratory of Virology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.ORCID 0000-0001-5734-7601
Clarice Weis ArnsLaboratory of Virology, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Pedro Pires Goulart GuimarãesDepartment of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Guilherme Mattos Jardim CostaDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Gustavo Batista de MenezesDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Cristina GuatimosimDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Glauber Santos Ferreira da SilvaDepartment of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Thiago Moreno L SouzaNational Institute for Science and Technology on Innovation on Diseases of Neglected Populations (INCT/IDNP), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, RJ, Brazil.
Breno Rocha BarrioniDepartment of Metallurgical Engineering and Materials, Federal University of Minas Gerais, School of Engineering, Belo Horizonte, Brazil.
Marivalda de Magalhães PereiraDepartment of Metallurgical Engineering and Materials, Federal University of Minas Gerais, School of Engineering, Belo Horizonte, Brazil.
Lirlândia Pires de SousaDepartment of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Mauro Martins TeixeiraDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.
Vivian Vasconcelos CostaDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Geraisgrid.8430.f, Belo Horizonte, MG, Brazil.ORCID 0000-0002-0175-642X
Universidade Federal de Minas Gerais · BRFundação Oswaldo Cruz · BRUniversidade Estadual de Campinas (UNICAMP) · BRUniversidade Iguaçu · BR

Funding

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 88887.507173/2020-00Ferring Research Institute (FRI) FIN0042393Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 2019/01255-9
6 · The paper itself

Abstract

The 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)

Indexed as

Disease Models, AnimalAnimalsCell LineContainment of BiohazardsCoronavirus InfectionsCytokinesHumansInflammationLiverLungMiceMurine hepatitis virusSARS-CoV-2Signal TransductionTumor Necrosis Factor-alphaVirus ReplicationCytokinesTumor Necrosis Factor-alphaanimal modelbetacoronavirusCOVID-19lung infectionMHV-3tumor necrosis factor

Identifiers

PMID34495692
PMCPMC8549505
OpenAlexW3198503168

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.