Emerging SARS-CoV-2 variants expand species tropism to murines

Abstract

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.

Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift

“…1b and Extended Data Fig. 6b), consistent with previous reports 23,24 . Conversely, our assay did not detect any binding of the Wuhan-Hu-1, Delta, or K417N RBDs to mouse ACE2.…”

“…The presence of the N501Y mutation has previously been described to enable some SARS-CoV-2 VOC to infect mice 23 . Since Omicron carries the N501Y mutation, along with 14 other RBD mutations, we investigated whether the Omicron RBD binds mouse ACE2 using surface plasmon resonance (SPR) (Fig.…”

Origin and evolutionary analysis of the SARS-CoV-2 Omicron variant

“…A mouse-adapted strain at passage 6 (MASCp6), which has an N501Y mutation, was shown to have increased infectivity in the lung during serial passaging in BALB/c mice [15] . Another study showed that three SARS-CoV-2 VOCs, namely B.1.1.7 and two other N501Y-carrying variants, B.1.351 and P.3, can infect mice [16] .…”

Attenuated replication and pathogenesis of SARS-CoV-2 B.1.1.529 Omicron

“…3c). Since the Omicron variant also carries the N501Y mutation, which allows the infection of wildtype mice and rats as we and others previously reported 19 , we additionally side-by-side characterized the replication of the N501Y-carrying Alpha and Omicron variant in wildtype C57B6 mice.…”