In Vitro and In Vivo Models for Studying SARS-CoV-2, the Etiological Agent Responsible for COVID-19 Pandemic

Rosa, Rafael Borges; Dantas, Willyenne Marília; Nascimento, Jéssica Catarine Frutuoso do; Silva, Murilo Vieira da; Oliveira, Ronaldo N. de; Pena, Lindomar

doi:10.3390/v13030379

Cited by 57 publications

(57 citation statements)

References 126 publications

(166 reference statements)

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“…Penetration routes can occur through damaged olfactory epithelium or via infected monocytes through compromised BBB later in the course of the disease. The neuropathology induced in this animal model makes it more suitable to further elaborate on neuropathogenesis of COVID-19 when compared to the Syrian hamster model which develop marked respiratory disease [33].…”

Section: Plos Pathogensmentioning

confidence: 99%

SARS-CoV-2 infection, neuropathogenesis and transmission among deer mice: Implications for spillback to New World rodents

et al. 2021

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Coronavirus disease-19 (COVID-19) emerged in late 2019 in China and rapidly became pandemic. As with other coronaviruses, a preponderance of evidence suggests the virus originated in horseshoe bats (Rhinolophus spp.) and may have infected an intermediate host prior to spillover into humans. A significant concern is that SARS-CoV-2 could become established in secondary reservoir hosts outside of Asia. To assess this potential, we challenged deer mice (Peromyscus maniculatus) with SARS-CoV-2 and found robust virus replication in the upper respiratory tract, lungs and intestines, with detectable viral RNA for up to 21 days in oral swabs and 6 days in lungs. Virus entry into the brain also occurred, likely via gustatory-olfactory-trigeminal pathway with eventual compromise to the blood-brain barrier. Despite this, no conspicuous signs of disease were observed, and no deer mice succumbed to infection. Expression of several innate immune response genes were elevated in the lungs, including IFNα, IFNβ, Cxcl10, Oas2, Tbk1 and Pycard. Elevated CD4 and CD8β expression in the lungs was concomitant with Tbx21, IFNγ and IL-21 expression, suggesting a type I inflammatory immune response. Contact transmission occurred from infected to naive deer mice through two passages, showing sustained natural transmission and localization into the olfactory bulb, recapitulating human neuropathology. In the second deer mouse passage, an insertion of 4 amino acids occurred to fixation in the N-terminal domain of the spike protein that is predicted to form a solvent-accessible loop. Subsequent examination of the source virus from BEI Resources determined the mutation was present at very low levels, demonstrating potent purifying selection for the insert during in vivo passage. Collectively, this work has determined that deer mice are a suitable animal model for the study of SARS-CoV-2 respiratory disease and neuropathogenesis, and that they have the potential to serve as secondary reservoir hosts in North America.

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Section: Plos Pathogensmentioning

confidence: 99%

SARS-CoV-2 infection, neuropathogenesis and transmission among deer mice: Implications for spillback to New World rodents

et al. 2021

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“…This result, together with the data obtained from other studies regarding the SARS-CoV-2 infection response in ferrets after injection of different viral loads, demonstrated that the virus could replicate in the upper respiratory tract of ferrets, showing a disease pattern similar to that of humans [ 65 ]. In addition, unlike mice and rats, ferrets exhibit the cough reflex; as coughing is the most frequently reported symptom in cases of SARS-CoV-2 infection, these animals represent promising models for this virus [ 68 ].…”

Section: Ferrets Models For Sars-cov-2mentioning

confidence: 99%

Current State of Knowledge about Role of Pets in Zoonotic Transmission of SARS-CoV-2

Dróżdż

Krzyżek

Dudek

et al. 2021

Viruses

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Pets play a crucial role in the development of human feelings, social life, and care. However, in the era of the prevailing global pandemic of COVID-19 disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many questions addressing the routes of the virus spread and transmission to humans are dramatically emerging. Although cases of SARS-CoV-2 infection have been found in pets including dogs, cats, and ferrets, to date there is no strong evidence for pet-to-human transmission or sustained pet-to-pet transmission of SARS-CoV-2. However, an increasing number of studies reporting detection of SARS-CoV-2 in farmed minks raises suspicion of potential viral transmission from these animals to humans. Furthermore, due to the high susceptibility of cats, ferrets, minks and hamsters to COVID-19 infection under natural and/or experimental conditions, these animals have been extensively explored as animal models to study the SARS-CoV-2 pathogenesis and transmission. In this review, we present the latest reports focusing on SARS-CoV-2 detection, isolation, and characterization in pets. Moreover, based on the current literature, we document studies aiming to broaden the knowledge about pathogenicity and transmissibility of SARS-CoV-2, and the development of viral therapeutics, drugs and vaccines. Lastly, considering the high rate of SARS-CoV-2 evolution and replication, we also suggest routes of protection against the virus.

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“…Similarly, in ferrets, the disease is relatively mild, and virus replication is mainly observed in the upper respiratory tract ( Shi et al, 2020 ). In addition, SARS-CoV-2 rapidly acquires spike protein mutations in ferrets as a result of critical species-specific differences in ACE2 receptor interactions ( Richard et al, 2020 ), showing the complexity of the response to viral infection in different animal hosts ( Leist et al, 2020 ; Rosa et al, 2021 ). All these models are costly and require specialised animal BSL-3 facilities.…”

Section: Introductionmentioning

confidence: 99%

Advancing lung organoids for COVID-19 research

Vaart

Lamers

Haagmans

et al. 2021

Disease Models &Amp; Mechanisms

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The COVID-19 pandemic has emphasised the need to develop effective treatments to combat emerging viruses. Model systems that poorly represent a virus' cellular environment, however, may impede research and waste resources. Collaborations between cell biologists and virologists have led to the rapid development of representative organoid model systems to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that lung organoids, in particular, have advanced our understanding of SARS-CoV-2 pathogenesis, and have laid a foundation to study future pandemic viruses and develop effective treatments.

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In Vitro and In Vivo Models for Studying SARS-CoV-2, the Etiological Agent Responsible for COVID-19 Pandemic

Cited by 57 publications

References 126 publications

SARS-CoV-2 infection, neuropathogenesis and transmission among deer mice: Implications for spillback to New World rodents

SARS-CoV-2 infection, neuropathogenesis and transmission among deer mice: Implications for spillback to New World rodents

Current State of Knowledge about Role of Pets in Zoonotic Transmission of SARS-CoV-2

Advancing lung organoids for COVID-19 research

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