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.
Dear Editor, The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a serious threat to global public health, and is imposing severe burdens on human society. Several candidate vaccines against SARS-CoV-2 are now undergoing clinical trials. The Spike (S) protein of SARS-CoV-2 is widely considered as a promising antigen. However, limited information about the protective immune response against SARS-CoV-2 has been reported. 1 In vivo or in natura data of the immune response in patients, including major immune responses to S protein, are currently lacking. The development of effective and safe vaccines against SARS-CoV-2 is urgently needed because of some potential adverse events including antibodydependent enhancement (ADE), 2 which might be difficult to avoid in current vaccine designs. Therefore, it is important to mine serological information from COVID-19 patients. In this study, we analysed the correlation between S-or Nucleocapsid (N) protein-specific antibody
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