Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy

Gu, Huiying; Chen, Qi; Guan, Yang; He, Lihua; Fan, Hang; Deng, Yong-Qiang; Wang, Yanxiao; Teng, Yue; Zhao, Zhongpeng; Cui, Yu‐Jun; Li, Yuchang; Li, Xiaofeng; Li, Jiangfan; Zhang, Nana; Yang, Xiaolan; Chen, Shao-Long; Zhao, Guangyu; Wang, Xiliang; Luo, Di; Wang, Hui; Li, Yan; Han, Gencheng; He, Yuxian; Zhou, Xiaojun; Geng, Shusheng; Sheng, Xiaoli; Shi, Bojiang; Sun, Shihui; Qin, Cheng‐Feng; Zhou, Yusen

doi:10.1101/2020.05.02.073411

Cited by 36 publications

(40 citation statements)

References 30 publications

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“…The spike protein of SARS-CoV-2 can be modified to gain effective binding to murine ACE2. One strategy is sequential passaging of SARS-CoV-2 in mouse lung tissue 8 . This method is successful because RNA virus populations consist of a mutant swarm of closely related viral quasispecies.…”

Section: Virus Adaptation To Mace2mentioning

confidence: 99%

Animal models for COVID-19

Muñoz‐Fontela

Dowling

Funnell

et al. 2020

Nature

777

810

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This is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

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Section: Virus Adaptation To Mace2mentioning

confidence: 99%

Animal models for COVID-19

Muñoz‐Fontela

Dowling

Funnell

et al. 2020

Nature

777

810

View full text Add to dashboard Cite

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“…Productive SARS-CoV-2 infection was shown in non-human primates, which developed respiratory disease recapitulating moderate disease as observed in humans 11-14 . Mice are not naturally susceptible to SARS-CoV-2, but mouse-adapted virus strains have been developed and used in BALB/c mice 15,16 . Moreover, transgenic mice expressing hACE2 represent a lethal SARS-CoV-2 infection model resulting in significant weight loss and permitting robust virus replication in the respiratory tract including the lungs 17 .…”

Section: Main Textmentioning

confidence: 99%

Age-dependent progression of SARS-CoV-2 infection in Syrian hamsters

Osterrieder

Bertzbach

Dietert

et al. 2020

Preprint

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22In late 2019, an outbreak of a severe respiratory disease caused by an emerging 23 coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans 1 . 24Complete understanding of COVID-19, the multi-faceted disease caused by SARS-CoV-25 2, requires suitable small animal models, as does the development and evaluation of 26 vaccines and antivirals 2 . Because age-dependent differences of COVID-19 were identified 27 in humans 3 , we compared the course of SARS-CoV-2 infection in young and aged Syrian 28 hamsters. We show that virus replication in the upper and lower respiratory tract was 29 independent of the age of the animals. However, older hamsters exhibited more 30 pronounced and consistent weight loss. In situ hybridization in the lungs identified viral 31 RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. 32Histopathology revealed clear age-dependent differences, with young hamsters launching 33 earlier and stronger immune cell influx than aged hamsters. The latter developed 34 conspicuous alveolar and perivascular edema, indicating vascular leakage. In contrast, 35we observed rapid lung recovery at day 14 after infection only in young hamsters. We 36propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 37 vaccines and treatments may yield valuable information as this small-animal model 38 appears to mirror age-dependent differences in human patients.

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“…Finally, we restricted our analyses to one strain of SARS-CoV-2, but other strains may have evolved with mutations that give more complementary interfaces. For example, recent work suggests SARS-CoV-2 can readily adapt to infect mice following serial passages [66].…”

Section: Figure 6: Mammals That Humans Come Into Contact With That Armentioning

confidence: 99%

SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals

Bordin

Waman

et al. 2020

Preprint

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SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated their relative energies, correlated these energies to COVID-19 infection data, and analysed structural interactions. We predict that known mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but not fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.

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Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy

Cited by 36 publications

References 30 publications

Animal models for COVID-19

Animal models for COVID-19

Age-dependent progression of SARS-CoV-2 infection in Syrian hamsters

SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals

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