Syrian Hamster as an Animal Model for the Study on Infectious Diseases

Miao, Jinxin; Chard, Louisa S.; Wang, Zhimin; Wang, Yaohe

doi:10.3389/fimmu.2019.02329

Cited by 85 publications

(83 citation statements)

References 164 publications

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“…Our results indicate that the golden Syrian hamster is a suitable experimental animal model for SARS-CoV-2 virus, as there is efficient viral replication in the upper and lower respiratory epithelial cells, efficient transmission from inoculated donors to co-housed naïve contacts, apparent clinical signs with greater than 10% weight loss in inoculated and naturally-infected hamsters. Hamsters are easy to handle with available reagents that can support immunological studies for vaccine development [25][26][27] .…”

Section: Resultsmentioning

confidence: 99%

Pathogenesis and transmission of SARS-CoV-2 virus in golden Syrian hamsters

Sia

Yan

Chin

et al. 2020

Preprint

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A pandemic caused by the novel SARS-CoV-2 virus with high nucleotide identity to SARS-CoV and SARS-related coronaviruses detected in horseshoe bats is spreading across the world and impacting the healthcare systems and global economy1,2. A suitable small animal model is urgently needed to support the development of vaccines and antiviral treatments against the SARS-CoV-2 virus. We report the pathogenesis and transmissibility of the SARS-CoV-2 in the golden Syrian hamster model. The SARS-CoV-2 virus replicated in the epithelial cells of respiratory and gastrointestinal tracts. Immunohistochemistry demonstrated viral antigens in the areas of lung consolidation on day 2 and 5 post- inoculation, followed by rapid viral clearance and tissue repairing on day 7. Viral antigen was also detected in the epithelial cells of duodenum without apparent inflammatory response on day 2. Notably, we observed that the SARS-CoV-2 virus can be transmitted efficiently from the inoculated hamsters to co-housed naïve contact hamsters. The inoculated hamsters and naturally-infected hamsters lost greater than 10% of the body weight, and all animals recovered with the detection of neutralizing antibodies within 14 days. Our results suggest that SARS-CoV-2 infection in golden Syrian hamsters resemble features found in human patients with mild infections.Authors Sin Fun Sia, Li-Meng Yan, and Alex WH Chin contributed equally to this work.

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Section: Resultsmentioning

confidence: 99%

Pathogenesis and transmission of SARS-CoV-2 virus in golden Syrian hamsters

Sia

Yan

Chin

et al. 2020

Preprint

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“…Nonhuman primate models have proven to be highly valuable for other infectious diseases but are expensive to maintain and numbers of experimental animals are limited. Our results provide an extended list of potential animal models for SARS-CoV-2 infection and pathogenesis, including large animals maintained for biomedical and agricultural research (e.g., domesticated sheep and cattle), and Chinese hamster and Syrian/golden hamster ( 47 ), which may be preferred due to their easier handling and already established value as models for other human diseases caused by viruses ( 69 ).…”

Section: Discussionmentioning

confidence: 99%

Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates

Damas

Hughes

Keough

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

580

641

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The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (frequency <0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.

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“…Our findings are consistent with a recent report 27 while the current study was under peer review. Hamsters are easy to handle and there are reagents to support immunological studies for vaccine development [28][29][30] . The results also highlighted similarity and differences between the SARS-CoV and SARS-CoV-2 in the hamster model.…”

Section: Pathogenesis and Transmission Of Sars-cov-2 In Golden Hamstersmentioning

confidence: 99%

Pathogenesis and transmission of SARS-CoV-2 in golden hamsters

Sia

Yan

Chin

et al. 2020

Nature

1,348

158

1,455

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SARS-CoV-2, a novel coronavirus with high nucleotide identity to SARS-CoV and SARS-related coronaviruses detected in horseshoe bats, has spread across the world and impacted global healthcare systems and economy 1,2 . A suitable small animal model is needed to support vaccine and therapy development. We report the pathogenesis and transmissibility of the SARS-CoV-2 in golden Syrian hamsters. Immunohistochemistry demonstrated viral antigens in nasal mucosa, bronchial epithelial cells, and in areas of lung consolidation on days 2 and 5 post-inoculation (dpi), followed by rapid viral clearance and pneumocyte hyperplasia on 7 dpi. Viral antigen was also found in the duodenum epithelial cells with viral RNA detected in feces. Notably, SARS-CoV-2 transmitted efficiently from inoculated hamsters to naïve hamsters by direct contact and via aerosols. Transmission via fomites in soiled cages was less efficient. Although viral RNA was continuously detected in the nasal washes of inoculated hamsters for 14 days, the communicable period was short and correlated with the detection of infectious virus but not viral RNA. Inoculated and naturally-infected hamsters showed apparent weight loss, and all animals recovered with the detection of neutralizing antibodies. Our results suggest that SARS-CoV-2 infection in golden Syrian hamsters resemble features found in humans with mild infections.SARS-CoV-2 was first detected from a cluster of pneumonia patients in Wuhan, Hubei Province, China in December 2019. Although 55% of the initial cases were linked to one seafood wholesale market where wild animals were also sold 3 , multiple viral (sustained human-to-human transmissibility by symptomatic and pre-symptomatic patients 4 ) and ecological factors (extensive domestic and international travel during Chinese Lunar New Year) have contributed to the rapid global spread of the virus. The clinical spectrum of patients with the novel coronavirus disease (COVID-19) is wide, 19% of 72,314 symptomatic patients in China progressed to severe and critical illness 5 with an estimated 1.4% symptomatic case fatality risk 6 . There is no approved vaccine or treatment against SARS-CoV-2, and the available interventions including country lock-down and social distancing have severely disrupted the global supply chain and economy.A suitable animal model is essential for understanding the pathogenesis of this disease and for evaluating vaccine and therapeutic candidates. Previous animal studies on SARS-CoV suggested the importance of the interaction between the viral spike protein and the host angiotensin converting enzyme 2 (ACE2) receptors 7-10 as well as age and innate immune status of the animals 11-14 in pathogenesis. As with SARS-CoV, the spike protein of SARS-CoV-2 also utilizes ACE2 receptors that are distributed predominantly in the epithelial cells of the lungs and small intestine to gain entry into epithelial cells for viral replication 1,15 . SARS-CoV-2 showed good binding for human ACE2 but limited binding to murine ACE2 1 , which has limited...

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Syrian Hamster as an Animal Model for the Study on Infectious Diseases

Cited by 85 publications

References 164 publications

Pathogenesis and transmission of SARS-CoV-2 virus in golden Syrian hamsters

Pathogenesis and transmission of SARS-CoV-2 virus in golden Syrian hamsters

Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates

Pathogenesis and transmission of SARS-CoV-2 in golden hamsters

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