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Published on: November 5, 2021
Emerging SARS-CoV-2 variants expand species tropism to murines
Huiping Shuai1, Jasper Fuk-Woo Chan2, Terrence Tsz-Tai Yuen3
1State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China; Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
Background:
Wildtype mice are not susceptible to SARS-CoV-2 infection. Emerging SARS-CoV-2 variants, including B.1.1.7, B.1.351, P.1, and P.3, contain mutations in spike that has been suggested to associate with an increased recognition of mouse ACE2, raising the postulation that these SARS-CoV-2 variants may have evolved to expand species tropism to wildtype mouse and potentially other murines. Our study evaluated this possibility with substantial public health importance.
Methods:
We investigated the capacity of wildtype (WT) SARS-CoV-2 and SARS-CoV-2 variants in infecting mice (Mus musculus) and rats (Rattus norvegicus) under in vitro and in vivo settings. Susceptibility to infection was evaluated with RT-qPCR, plaque assays, immunohistological stainings, and neutralization assays.
Findings:
Our results reveal that B.1.1.7 and other N501Y-carrying variants but not WT SARS-CoV-2 can infect wildtype mice. High viral genome copies and high infectious virus particle titres are recovered from the nasal turbinate and lung of B.1.1.7-inocluated mice for 4-to-7 days post infection. In agreement with these observations, robust expression of viral nucleocapsid protein and histopathological changes are detected from the nasal turbinate and lung of B.1.1.7-inocluated mice but not that of the WT SARS-CoV-2-inoculated mice. Similarly, B.1.1.7 readily infects wildtype rats with production of infectious virus particles.
Interpretation:
Our study provides direct evidence that the SARS-CoV-2 variant, B.1.1.7, as well as other N501Y-carrying variants including B.1.351 and P.3, has gained the capability to expand species tropism to murines and public health measures including stringent murine control should be implemented to facilitate the control of the ongoing pandemic.
Funding:
A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
Insights
Emerging SARS-CoV-2 variants like B.1.1.7 can now infect wildtype mice and rats, unlike the original virus. This finding highlights the need for enhanced control measures in animal populations to manage the pandemic.
Area of Science:
- Virology
- Infectious Diseases
- Public Health
Background:
- Wildtype mice are typically resistant to SARS-CoV-2.
- New SARS-CoV-2 variants (B.1.1.7, B.1.351, P.1, P.3) possess spike protein mutations potentially enabling mouse ACE2 recognition.
- This raises concerns about expanded species tropism to rodents.
Purpose of the Study:
- To investigate the susceptibility of wildtype mice and rats to SARS-CoV-2 infection.
- To determine if emerging SARS-CoV-2 variants have evolved to infect murine models.
Main Methods:
- In vitro and in vivo infection studies using wildtype SARS-CoV-2 and variants.
- Evaluation of infection via RT-qPCR, plaque assays, and immunohistochemistry.
- Neutralization assays were also performed.
Main Results:
- The B.1.1.7 variant, and other N501Y-carrying variants, successfully infected wildtype mice and rats.
- High viral loads and infectious particles were detected in the respiratory tracts of infected mice.
- Histopathological changes and viral nucleocapsid protein expression confirmed infection in B.1.1.7-inoculated mice.
Conclusions:
- The SARS-CoV-2 B.1.1.7 variant, along with other N501Y variants, can infect murines.
- These findings underscore the expanded host range of SARS-CoV-2 variants.
- Stringent control measures for rodents are recommended to aid pandemic control.
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