Animal models of SARS-CoV-2 transmission

Vries, Rory D. de; Rockx, Barry; Haagmans, Bart L.; Herfst, Sander; Swart, Rik L. de

doi:10.1016/j.coviro.2021.06.007

Cited by 30 publications

(22 citation statements)

References 123 publications

(146 reference statements)

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“…The hACE2 expression in K18-hACE2 strain is driven by the human cytokeratin-18 (K18) gene promoter, which results in a different hACE2 physiological distribution pattern from that of human 18 . In addition, mice are unsuitable for SARS-CoV-2 transmission investigations and the genetic disparities between mouse and human immune systems also make them less appealing than non-human primates for studying vaccine-induced immune responses 56 , 57 .…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains

et al. 2021

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SARS-CoV-2 variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 (beta) show increased transmissibility and enhanced antibody neutralization resistance. Here we demonstrate in K18-hACE2 transgenic mice that B.1.1.7 and B.1.351 are 100-fold more lethal than the original SARS-CoV-2 bearing 614D. B.1.1.7 and B.1.351 cause more severe organ lesions in K18-hACE2 mice than early SARS-CoV-2 strains bearing 614D or 614G, with B.1.1.7 and B.1.351 infection resulting in distinct tissue-specific cytokine signatures, significant D-dimer depositions in vital organs and less pulmonary hypoxia signaling before death. However, K18-hACE2 mice with prior infection of early SARS-CoV-2 strains or intramuscular immunization of viral spike or receptor binding domain are resistant to the lethal reinfection of B.1.1.7 or B.1.351, despite having reduced neutralization titers against these VOC than early strains. Our results thus distinguish pathogenic patterns in K18-hACE2 mice caused by B.1.1.7 and B.1.351 infection from those induced by early SARS-CoV-2 strains, and help inform potential medical interventions for combating COVID-19.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains

et al. 2021

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“…Studies have also been performed in animals in vivo , including species that are naturally susceptible to SARS-CoV-2 [ 50 , 76 , 77 • ]. In hamsters, SARS-CoV-2 infection triggers an ISG signature in the lungs [ 78 , 79 , 80 ].…”

Section: Type I Ifn Immunity In Animal Models Naturally Susceptible To Sars-cov-2mentioning

confidence: 99%

Type I interferons and SARS-CoV-2: from cells to organisms

Bastard

Zhang

et al. 2022

Current Opinion in Immunology

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Type I interferons (IFNs) have broad and potent antiviral activity. We review the interplay between type I IFNs and SARS-CoV-2. Human cells infected with SARS-CoV-2 in vitro produce low levels of type I IFNs, and SARS-CoV-2 proteins can inhibit various steps in type I IFN production and response. Exogenous type I IFNs inhibit viral growth in vitro . In various animal species infected in vivo , type I IFN deficiencies underlie higher viral loads and more severe disease than in control animals. The early administration of exogenous type I IFNs improves infection control. In humans, inborn errors of, and auto-antibodies against type I IFNs underlie life-threatening COVID-19 pneumonia. Overall, type I IFNs are essential for host defense against SARS-CoV-2 in individual cells and whole organisms.

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“…Transmission rates in ferrets vary amongst spike glycoprotein mutations seen with different variants, with higher transmissibility of S(614G) over S(614D) glycoprotein structures [98]. Airborne transmission of SARS-CoV-2 was also shown [3,85,96]; however, this transmission appeared less efficient and diminished at distances greater than 1 m [3,99]. Despite multiple studies supporting direct and indirect transmission between ferrets, differences in disease pathogenesis and outcomes are noted between studies.…”

Section: Ferretsmentioning

confidence: 99%

“…Given their susceptibility to SARS-CoV-2, histopathological changes, detectable viral loads, and shedding from the respiratory tract during infection, ferrets continue to be a highly regarded model for asymptomatic or mild COVID-19 [3,79]. Unfortunately, the lack of pulmonary viral replication and edema or the development of ARDS in ferrets suggest a major limitation for the study of lung pathology with COVID-19 [106].…”

Section: Ferretsmentioning

confidence: 99%

“…For these reasons, animal models are the critical bridge to the development and evaluation of prophylactic treatments, specifically drugs, vaccines, and therapeutic agents, and are required to elucidate key mechanisms underlying pathology in vivo. Traditional lab animal species, including mice and nonhuman primates (NHPs), have been used extensively in SARS-CoV-2 research, and their involvement and utility has been thoroughly cataloged [2][3][4][5][6][7][8][9][10][11][12][13]. This review, however, focuses on the contribution of nontraditional animal models to understanding the pathophysiology and transmission kinetics of SARS-CoV-2 infection, as well as their practicality in a research setting.…”

Section: Introductionmentioning

confidence: 99%

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Thinking Outside the Box: Utilizing Nontraditional Animal Models for COVID-19 Research

Gunasekara

Selvan

Miller

et al. 2022

IJTM

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The ongoing COVID-19 pandemic continues to affect the lives, wellbeing, and stability of communities worldwide. The race to save human lives is critical, and the development of useful translational animal models to elucidate disease pathogenesis and prevention, and to test therapeutic interventions, is essential to this response. However, significant limitations exist with the currently employed animal models that slow our ability to respond to the pandemic. Non-human primates serve as an excellent animal model for SARS-CoV-2 disease and interventions, but the availability of these animals is scarce, and few facilities are able to house and utilize this model. Adapted murine models are accessible and improving but lack natural hACE-2 receptors and are only moderate representatives of human COVID-19 disease, transmission, and immune responses. On the other hand, there are several animal species that are both naturally and experimentally infected, such as domestic cats, hamsters, ferrets, and mink. Several of these have proven animal-to-animal transmission and evidence of significant clinical and histopathologic disease that mimics acute COVID-19 in humans. Mobilizing these nontraditional animal models could have a crucial role in SARS-CoV-2 research efficiency and impact. This review focuses on what is known about these nontraditional animal models, including their immune responses to SARS-CoV-2 infection, evidence of clinical and histopathologic disease, transmission potential, and the practicality of each model in a research setting. Comparative insight into these animal models for COVID-19 can strengthen the efforts to mitigate this pandemic.

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Animal models of SARS-CoV-2 transmission

Cited by 30 publications

References 123 publications

SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains

SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains

Type I interferons and SARS-CoV-2: from cells to organisms

Thinking Outside the Box: Utilizing Nontraditional Animal Models for COVID-19 Research

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